SYSTOPLC LABORATORIES (PVT.) LTD. ETC. ETC.versusDR. PREM GUPTA AND ORS. ETC. ETC.

        SYSTOPlC LABORATORIES (PVT.) LTD. ETC. ETC.                            A
                                     v.
             DR. PREM GUPTA AND ORS. ETC. ETC.

                         SEPTEMBER 22, 1993

      [M.N. VENKATACHALIAH CJ AND S.C. AGRAWAL, J.]                            B

       Drngs & Cosmetics Act, 1940: Section 26A-Notifications issued there-
under-Notification dated 3. 11.1988 amending earlier notification dated
23. 7.1983-Jtem 14 of the dlugs substituted-Effect of prohibiting in public
interest the manufacture of steroid in fu:ed dose combinations for treatment   c
of asthmir--On the basis of expert opinion Central Govemment satisfied that
Use of such drngs involve risk to human beings-Validity of the notifica-
tion-Fresh material in support of revocation of ban-Consideration of by the
Technical Advisory Board-Directions issued.

      Constitution of India, 1950:                                             D

      Art. 19( 1)(g)-Notification dated 3. 11.1988 issued under S.26A of
Drngs & Cosmetics Act. 194o-Ban on manufacture and sale of steroids in
fu:ed dose combinations for treatment of asthma-Whether imposes un-
reasonable restriction and violative of
                                                                               E
      In exercise of the powers conferred by Section 26-A of the Drugs &
Cosmetics Act, 1940, the Central Government issued a notification dated
3.11.1988 whereby the earlier notification dated 23.7.1983 was amended
and item no.14 of the drugs specified in the Table was substituted. On the
basis of the opinion given by an Expert Committee that long term use of F
steroids in fixed dose combinations for treatment of asthma involved risk
to human beings and that there was no therapeutic justification for such
formulations, the Central Government felt it was necessary and expedient
in public interest to prohibit the manufacture of the said drugs, and
accordingly it issued the said notification. The manufacture and sale or' G
fixed dose combination of corticosteroids with any other drug for internal
use were completely prohibited and the earlier exemption of such fixed
dose combinations for treatment of asthma was withdrawn.

     Various manufacturers of said fixed dose combinations of the said
drug filed Writ Petitions in different High Court. One such Writ petition H
                                     385
    386                  SUPREME COURT REPORTS (1993] SUPP. 2 S.C.R.

A was dismissed by a High Court and the Special Leave Petition filed against
    it was dismissed by this Court. Following this another High Court also
    dismissed the Writ Petitions filed before it against which the present
    appeal were filed. The Transferred Cases were the Writ Petitions filed in
    another High Court. A manufacturer who was not manufacturing such a
    drug but has submitted its application for permission to manufacture the
B   drug had filed a Writ Petition before this Court. All these appeals/ peti·
    tions challenge the validity of the notification dated 3.11.1988.

        On behalf of the appellants/petitioners, it was contended inter alia
  that scientific data in the form of published paper in the various medical
C journals showed that fixed dose combination of a corticosteroid and an
  antihistamine has been highly beneficial for the treatment of asthma; that
  the said studies revealed that the patient could obtain an equally effective
  treatment by consuming half the quantity of steroid, and that the com·
  bination has well-recognised synergistic and potentiating properties and
  characteristics and has been more effective.
D
        On behalf of the respondents, extracts from medical treatises and
  foreign medical journals were filed to show that fixed dose combination of
  cortisteroids and anti-histamines was irrational because anti-histamines
  do not have any role to play in asthma management and that in respect of
E bronchial asthma, the standard treatment viz. broncho·dilator alone may
  not give the desired result and corticosteroids may be resorted to as a
  therapy but the dosage required was to be regulated carefully. It was
  contended that at no stage fixed dose combinations of corticosteroids with
  other drugs were recommended in the treatment of Asthma and that such
  combination were either withdrawn or never introduced for marketing in
F countries like USA, UK etc. As regards the studies and reports relied on
  by the appellants/petitioners, the Respondent contended that they were
  based on research done on animal models and no comparative study
  between corticosteroids alone and fixed dose combinations on human
  beings had been shown and many of the studies were not authentic or were
G obsolete; and that no standard book or authentic medical journal spoke
  about fixed dose combination of corticosteroids and other drugs in the
  management of asthma.

          Dismissing the matters, the Court

H         HELD : 1.1. The court cannot make an assessment about the relative
         SYSTOPIC LABORATORIES (P.) LTD. v. DR.1'. GUPTA               387

merits of the various studies and reports placed before it. Such an          A
evaluation is required to be done by the Central Government while exer-
cising its powers under Section 26A of the Drugs & Cosmetics Act, 1940
on the basis of expert advice and the Act makes provision for obtaining
such advice through the Board and the Drugs Consultative Committee
(DCC). [399-B]
                                                                             B
       1.2. A perusal of the minutes of the meetings of the Board, the
Sub-Committee of the DCC as Well as the Experts Committee shows that
the material submitted on behalf of the manufacturers of the drugs in
question was examined by the members and it cannot be said that there
h~S been no proper consideration of the said material by the Expert          c
Committee or the Sub-committee of th DCC. The complaint that experts
in clinical medicine were not associated with the Expert Committee was
not justified. [399-E-F]

       1.3. The experts did not consider it necessary to conduct clinical D
trials in respect of fixed dose combination of steroids with broncho·
dilators for systematic use. the petitioners and other manufacturers, if
they so desired, could have· submitted fresh material on clinical trials
conducted during the period subsequent to the notification dated July 23,
1983 in justification of their case before the experts. They did no, however,
do so and they only produced material which was anterior to the notifica- E
tion dated July 23, 1983. As to whether clinical trials should have been
conducted or not was primarily for the experts to decided and if the experts
felt that in respect of the drugs in question such clinical trials were not
necessary, it cannot be said that there has been no proper evaluation of
the material that was submitted by the manufactures before the Expert
Committee. [400-F-H]
                                                                              F

       2.1. The notification prohibiting the manufacture an sale of the drug
in question does not suffer from the vice of unreasonableness. In taking
this step the Central Government has moved in a cautious manner. In the
earlier notification dated July 23, 1983, whereby manufacture and sale of G
a number of drugs, including fixed dose combinations of certain drugs was
prohibited, an exception was made in respect of fixed dose combinations
of corticosteroids with other drugs for the treatment of asthma. At that
time also the DCC had expressed the view that fixed dose combinations of
corticosteroids with other drugs was' harmful as indiscriminate use of H
    388                  SUPREME COURT REPORTS (1993] SUPP. 2 S.C.R.

A   corticosteroids could produce serious side effects and in certain clinical
    conditions where administration of steroids is considered necessary, the
    drug can be prescribed separately. The Board, however, felt that so far as
    combination of steroids with other drugs for treatment of asthma are
    concerned, there was need for examining the matter in further detail and
B   getting wider opinion in the matter and therefore, it recommended that
    such combination may continue. [402-D-H]

          2.2. The matter was thereafter examined in detail by the sub-commit-
    tee of the DCC as well as the Experts Committee in 1987-88 and the
    representatives of the manufacturers were given adequate opportunity of
c   producing material in support of continued marketing of the said drugs
    and very were also personally heard. After taking into consideration all
    the relevant date that were made available, the Sub-Committee of Experts
    expressed the same view as was held by DCC earlier and they opined that
    fixed dose combinations of corticosteroids with any other drug should not
D   be allowed because in the recommended upper dosage limit the daily dose
    of corticosteroid often exceeds safe pharmacological limit for adreocortical
    suppression and that the combinations do not permit titration of the
    steroid doses which is often required in practice or the administration of
    the minimum daily dose once a day so as to avoid adrenocortical suppres-
E   sion. Hence the Board recommended that the fixed dose combinations of
    corticosteroids with other drugs for use in Asthma should be banned
    because asthma therapy is a long term therapy and corticosteroids in
    dosage when administered for longer periods are reported to cause more
    harm than good to the patients. [403-A-E]

F          2.3. While examining the reasonableness of the prohibition against
    manufacture and sale of the said drugs the harmful potentialities of the
    drugs have to be considered in the context of the conditions as prevalent
    in the country where, on account of illiteracy, people are not aware of the
    ill effects of the drugs available in the market and are often misled and
G misguided by quacks and inexperienced doctors. The less drastic course
    of permitting manufacture and sale of the drugs with a warning about its
    use would not be adequate to protect the general public from the harmful
    consequences. The Prohibition imposed by the impugned notification does
    not impose an unreasonable restriction and is therefore not violative of
I-I the right guaranteed under Article 19(1)(g) of the Constitution. [403-F-H]
           SYSTOPIC LABORATORIES (P.) LTD. v. DR. P, GUPTA               389

        State of Madras v. VG. Row, [1952) SCR 597 and Narendra Kumar           A
  and others v. The Union of India and Others, [1960) 2 SCR 375, relied on.

        Mohd. Faruk v. State of Madhya Pradesh and Others, [1970) 1 SCR
  156, referred to.

         3. Having regard to the observations made by this Court in its order   B
  dated January 6, 1992 in SLP (C) No. 1588 of 1989, the petitioners as well
  as other manufacturers who have filed writ petitions in the High Court
, and whose writ petitions were pending in the High Court were also ap·
  proach the Technical Advisory Board and produce any fresh material in
  support of their claim for revocation of the ban on manufacture and sale      C
  of fixed dose combination of corticosteroids with any drug for internal use
  for treatment of Asthma. The Board, while considering the matter would
  take into account such material. [404-B, CJ

         4. Since the interim directions issued by the Court were limited to
  production for a short period only on the basis of the average monthly D
  production, there was no reason to assume that large stocks of drugs was
  lying with the petitioners. In the circumstances, it would not be ap·
  propriate to give any direction regarding permitting the petitioners to sell
  existing stocks of the drug. [404-G)

        CIVIL APPELLATE JURISDICTION : Civil Appeal Nos. 2791-                  E
  2796 of 1992.

        From the Judgment and Order dated 3.6.1992 of Punjab and
  Haryana High Court in C.W.P. Nos. 6882/88, 1328/89, 1329/89, 1330/89,
  802/90 and 12556 of 1990.
                                                                                F
                                    WITH

       T.C. (C) Nos. 13-14/92, SLP(C) Nos. 9972 & 10745/92 and W.P. (C)
  No. 364/93.
                                                                                G
        R.F. Nariman, Vivek Sibal, Suman J. Khaitan, for Khaitan & Co., S.
  Ganesh, Ravinder Narian, Ms. Amrit Mitra, for JBD & Co., Ms. Kamini
  Jaiswal, Ms. Lily Thomas and P.N. Puri for the Appellants.

      V.R. Reddy, Addi. Solicitor General, V.C. Mahajan, R.N. Sachthey,
  Hemant Sharma, V.K. Verma, T.V. Ratnam, C.V.S. Rao, Mrs. Kawaljit H
    390                   SUPRE'A:E COURT REPORTS (1993) SUPP. 2 S.C.R.

A. Kochar, J.D. Jain, Badri Nath Babu, Anip Sachthey and Anil K. Jha for
    the Respondents.

          Vivek Sibbal, N.D.B. Raju and Ms. Kum Kum Sen for the Intervenor.

          Th,e Judgment of the Court was delivered by
B
           S.C. AGRAWAL, J. These cases raise common question involving
    challenge to the validity of the notification dated November 3, 1988 issued
    by the Government of India, whereby the earlier notification dated July 23,
    1983 was amended and item No. 14 of the drugs specified in the Table in
C   the said notification was substituted so as to prohibit completely the
    manufacture and sale of fixed dose combination of steroids with other
    drugs for internal use. The said notification has been issued in exercise of
    the power conferred by Section 26-A of the Drugs & Cosmetics Act, 1940
    (hereinafter referred to as 'the Act'). In the said notification, it has been
D   stated that the Central Government is now satisfied that long term use of
    steroids in fixed dose combinations for treatment of asthma is likely to
    involve risk to human beings and such formulations do not have therapeutic
    justification and further that it is necessary and expedient in public interest
    to prohibit the manufacture and sale of the said drugs.

E          A number of manufacturers, including the appellants in Civil Ap-
    peals Nos. 2791 - 96 of 1992 and the petitioners in SLP(C) Nos. 9972 and
    10745 of 1992 and Transferred Cases (C) Nos: 13 - 14 of 1992, filed writ
    petitions in various High Courts to challenge the validity of the said
    Notification. One of these writ petition (no. 364 of 1993), filed in the
F   Madras High Court by Micro Labs (P) Ltd., was dismissed by a Division
    Bench of the said High Court by judgment dated June 18, 1991 SLP (C)
    No. 1538 of 1991 filed against the said decision was also dismissed by this
    Court on January 6, 1992 with the following observations -

             "The special leave petition is dismissed. The petitioner, however,
G            will be permitted to make a fresh application for permitting
             manufacture and sale of drugs in question which will be considered
             by the Technical Board which will include one or more practising
             doctors specialising in treating Asthma cases. The inclusion may
             be in the form of membership or in advisory or any other ap-
H            propriate capacity"
SYSTOPICLABORATORIES (P.) LTD. v. DR. P. GUPTA[AGRAWAL,J.] 391

       Following the aforesaid decision of the Madras High Court in Micro A
 Labs' case (supra), a Division Bench of the High Court of Punjab &
 Haryana, by judgment dated June 3, 1992 dismissed a number of wrjt
petitions wherein the validity of the. notification dated November 3, 1988
had been challenged. Civil Appeals (C) Nos. 2791-96 of 1992 and SLP(C)
Nos. 9972 of 1992 and 10745 of 1992 are directed against the said decision B
of the High Court of Punjab and Haryana. Transferred Cases (C) Nos. 13
and 14 of 1992 relate to writ petition no. 1701 of 1984 [Fulford India
Limited and Another v. Dr. S.S. Gothoskar and Ors. and writ petition no.
1746 of 1984), U)ieth Laboratories Ltd. & Anr. v. Dr. S.S. Gothoskar & Ors.]
which were originally filed in the Bombay High Court. The appellants in
the appeals (who would referred to as the petitioners for the sake of C
convenience) as well as the petitioners in Special Leave Petitions and the
Transferred Cases have been manufacturing fixed does combinations of
corticosteroids with anti-histamines and corticosteroids with broncho-
dilators under different names. The petitioner in writ petition no. 364 of
1992, which has been filed under Article 32 of the Constitution, holds a D
licence granted by Director, Drugs Control Administration of the Govern-
ment of Andhra Pradesh for the manufacture and sale of medicines and
drugs. The said petitioner is not manufacturing the prohibited drugs but
has submitted an application for permission to manufacture the said drugs.

      Reference, at this stage, may be made to the relevant provisions of E
the Act. As stated in the preamble, the Act has been enacted to regulate
the import, manufacture, distribution and sale of drugs and medicines.
Section 5 of the Act provides for the constitution of the Drugs Technical
Advisory Board (hereinafter referred to as 'the Board') by the Central
Government to advise the Central Government and the State Governments p
on technical matters arising out of the administration of the Act and to
carry out the other functions assigned to it by the Act. Section 7 empowers
the Central Government to constitute and advisory committee to be called
as Drugs Consultative Committee (in short, DCC) to advise the Central
Government and the State Governments and the Board on any mater
tending to secure uniformity throughout India in the administration of the G
Act. Section 26A, which was introduced in the Act by Drugs Amendment
Act, 1982 (Act no. 68 of 1982), provides as under -

        "26A. Without prejudice to any other provisions contained in this
        Chapter, if the Central Government is satisfied, that the use of H
    392                   SUPREME COURT REPORTS (1993] SUPP. 2 S.C.R.

A           any drug or cosmetic is likely to involve any risk to human being
            or animals or that any drug does not have therapeutic value
            claimed or purported to be claimed for it or contains ingredients
            and in such quantity for which there is no therapeutic justification
            and that in the public interest it is necessary or expedient so to
            do, then the Government may, by notification in the official
B           Gazette, prohibit the manufacture, sale distribution of such drug
            or cosmetic".

          In 1979, the DCC had set up an Experts Committee as a Sub-
    committee of the DCC for screening the formulations of drugs prevalent
c   in the Indian market from the point of view of therapeutic rationale in
    order to weed out irrational/harmful combination of drugs. The Sub-Com-
    mittee examined a number of fixed dose combinations of drugs which did
    not appear to have adequate rationale or appeared to be harmful and made
    the following recommendation in respect of fixed combinations of steroids:

D           "Fixed dose combinations of steroids with any other category of
            drugs should not be allowed as they are considered harmful for
            the following reasons :

                 (a) The adrenal suppression accompanying steroid therapy
            leads to symptoms and signs of adrenal insufficiency, if the steroid
E
            is. abruptly withdrawn.

                (b) It is difficult to titrate the dose of a steroid when it is present
            in fixed dose combinations with other drugs."

F        The recommendations of the Sub-Committee were considered by the
    DCC in its meeting held on October 19, 1981 and in relation to steroid
    combinations the DCC took the following decision :

            "Fixed dose combinations of Steroids for internal use should not
            be allowed. However, for therapeutic convenience the industry
G           should be prevailed upon to make available preparations of
            steroids in lower strength e.g. Prednisolone Tablet 1 mg. Fixed
            dose combination of corticosteroids with other drugs are not
            justifiable as indiscriminate use of corticosteroids can produce
            serious side effects viz. fluid and electrolyte disturbances, hyper-
H           glycemia and glycosuria, increased susceptability to infection, in-
SYSTOPICLABORATORIES (P.) LTD. v. DR. P. GUPTA[AGRAWAL,J.] 393

        eluding tuberculosis, peptic ulcers, osteoporosis, a characteristic    A
        myopathy, Cuihing's habitus, hirsutism etc. In certain clinical con-
        ditions where administration of steroid is considered necessary,
        the drug can be prescribed separately".

      The recommendations of the DCC were considered by the Board at
its meeting held on December 31, 1981 and the Board made following             B
recommendation -

        "STEROID COMB/NA TIO NS :

           Fixed combinations of steroids with other drugs for internal use
        should not be allowed.                                                 C
           However, the Board felt that so far as combination of steroids
        with other drugs for the treatment of asthma are concerned there
        was a need for examining the matter in further details and getting
        wide medical opinion in the matter. The Board, therefore, felt that    D
        such combination may continue for the present".

      After the incorporation of Section 26-A in the Act, notification dated
July 23, 1983 was issued by the Government of India in the light of the
recommendations made by the Board and the manufacture and sale of 22
drugs were prohibited under Section 26-A of the Act. Out of these 22           E
drugs, items 2 to 17, including item 14, were fixed dose combinations of
certain drugs. Item 14 in the said notification was -

        "14. Fixed dose combination of Steroids for internal use except
        combination of Steroids with other drugs for the treatment of
        Asthma".                                                               F
     Similar exception had been made in item no. 15 relating to fixed
dose combinations of chloramphenicol for fixed dose combination of
Chloramphenicol and streptomycin.

      It appears that there was criticism in vario,us fora of the exemption G
granted for fixed dose combinations of Steroids for treatment of asthma
and medical critics opined that there is hardly a clinical situation when a
fixed does combination of corticosteroids with drugs like bronchodilators
are required. Taking note of the criticism the Sub-Committee of the DCC
at the meeting held on January 15, 1987 felt it necessary to review again H
    394                  SUPREME COURT REPORTS [1993] SUPP. 2 S.C.R.

A the fixed dose combination of corticosteroids and it was decided that the
  manufacturers of such drugs be asked to establish published evidence of
  rationality for continued marketing of such combinations. It was also
  decided that the experts should also be requested to participate in the next
  meeting. At the next meeting held no June 3, 1987 the Sub- committee was
B informed by the Chairman that the experts had desired that more technical
  data on the rationality/efficiency of the combination of drugs in the Indian
  context should be generated or asked for and the Sub-Committee decided
  that representatives of the manufacturers should be given a hearing to
  record their views at the next meeting and that this could be ensured by
C writing to Pharmaceutical Associations. A special meeting of experts to
  examine the views of the affected manufacturers who represented against
  withdrawal of certain formulations moving in the market was held on
  September 8, 1987. At the said meeting a summary of the view points of
  the manufacturers as well as a critical review on various submissions
  prepared by the Director General of Health Services was placed before
D the experts. At the said meeting the criteria/guidelines for evaluation of
   each category of formulation were evolved and it was decided that the
  experts would evaluate the various types of formulations after going
   through the written submissions furnished by the affected manufacturers.
   The original supporting date furnished by the manufacturers was also
E forwarded to the experts. At the meeting of experts and the members of
   the Sub- Committee held on October 16 and 17, 1987 the representations
   submitted by different firms against the notification on 12 categories of
   drugs as irrational or of doubtful efficiency were discussed by the repre-
   sentatives of the industry and the committee and thereafter the following
F recommendations were made -
             "F.D.C. of Conicosteroids with Bronchodilators/Antihistaminics for
             systemic use

                The Committee observed that the formulations moving in the
G            market when administered at the recommended daily dose exceeds
             the safety limit of cortiocosteroid besides there is no rationality of
             F.D.C. of Corticosteroids with bronchodilators/antihistaminics for
             the following reasons : -

H            (a) "FDC of Cortiosteroid with Bronchodilator
    SYSTOPICLABORATORIES (P.) LTD. v. DR. P. GUPTA[AGRAWAL,J.] 395

                 The recommended dose exceeds the adrenal suppression.                A
             Moreover such combinations limit the scope of titration of cor-
             ticosteroids which may be required in clinical situations. Such fixed
             dose combination should not be allowed.

             (b) F.fJ.C. of Corticosteroids wit~ antihistaminics
                                                                                      B
             Antihisfamim~s has no role in the· management of bronchial asthma
            as h'istiiini11.e ·is· released from s6nsitized mast cells in very high
            i;01kep.tratlon. near the target cells and antihistaminics cannot
            block such 'effect quantitatively. Besides many· more chemical
            mediat6rs are released in sensitized target cells not antagonised
            by anlihistaminics.
                                                                                      c
            There is a lack of published evidence to prove the higher efficacy
            of such combination over Corticosteroid alone. Such combinations
            should not be allowed."
                                                                                      D
r          The Sub-Committee at its meeting held on Jamtary 15-16, 1988,
    noticed that the experts have opined that little will be achieved by conduct-
    ing trial on these categories and have reiterated their earlier stand of
    recommending withdrawal of fixed dose combination of steroids with
    bronchodialtors for systematic use. The Sub-Committee has also recorded
    that the manufacturers of these formulations were asked through IDMA              E
    an OPPI to furnish evidence justifying their continued marketing of fixed
    dose combinations of corticosteroids with other drugs for internal use and
    the literature and any other information furnished by the manufacturers
    were examined by the expert groups and interested manufacturers were
    given an opportunity for pleading their case in person with the experts and       F
    that after going through the information and literature furnished by the
    manufacturers and after listening the various arguments, the experts had
    unanimously taken the following decision-

            "With regard to fixed dose combinations containing corticosteroids
            and bronchodilators/other drugs, the experts had opined that fixed G
            dose combinations of corticosteroids with any other drug for in-
            ternal use should not be allowed because in the recommended
            upper dosage limit the daily dose of corticosteroids often exceeds
            safe pharmacological limit for adrenocortical suppression. Besides,
            the combinations do not permit titration of the steroid doses which H
    396                  SUPREME COURT REPORTS (1993] SUPP. 2 S.C.R.

A           is often required in practice or the administration of the minimum
            daily dost once a day so as to avoid adrenocortical suppression.
            Moreover there is hardly any authentic reference ,to support that
            fixed dose combination of corticosteroids with bronchodilators or
            anti-histaminics are recommended in the treatnv:nt of asthma''.

B         The Sub-Committee expressed the following view :

            "In this context, it may be pertinent to mention that the.expert body
            and the DCC had also earlier held the same views now expressed
            by the expert group. As advised by the DTAB examina~ion ~f t~e
            above mentioned categories have been done and their rec01mnen•
c           dations with reasons are now placed before the DTAB fori,aking
            a final decision in the matter".

          The matter was thereafter considered by the Boara at its meeting
    held on April 22, 1988 and the following view was c;xpressed -
D
            "The Board agreed that the fixed dose combination of chloram-
            phenical and streptomycin should not be allowed to be marketed.

            After exchange of views amongst the members it was agreed that
            the fixed dose combinations of corticosteroids with other drugs for
E           use in asthma should be banned because asthma therapy is a long
            term therapy and corticosteroids even in low dosage when ad-
            ministered for longer periods are reported to cause more harm
            than good to the patients. The Board approved that the entry no.
            14 appearing in the notification GSR No. 578(E) dated 23.7.1983
            may be suitably amended''.
F
           Having regard to the aforesaid recommendations of the Board, the
    impugned notification dated November 3, 1988 was issued whereby item
    no. 14 contained in the earlier notification dated July 3, 1983 was sub-
    stituted as under -
G
            "Fixed dose combination of corticosteroids with any other drug for
            internal use''.

          As a result-0f the said notification dated November 3, 1988, manufac-
    ture and sale of fixed dose combination of corticosteroids with any other
H   drug for internal use have been completely prohibited and the earlier
SYSTOPICLABORATORIES (P.) LTD. v. DR. P. GUPTA[AGRAWAL,J.)397

exemption of such fixed dose combinations for treatment of asthma has          A
been withdrawn.

      In this context it rnay be mentioned that in with petition no. 3554 of
1988 filed by M/s. Roussel Pharmaceuticals pending before the Bomaby
High Court, the following observations were made by High Court in an           B
order dated February 21, 1989 -

        "the Government, even at this stage, may apply its mind afresh and
        hear all the persons concerned on this question and then take
        appropriate decision".
                                                                               c
        In view of the said observations, the matter of prohibition of fixed
 dose combination of steroids with other drugs for internal use was con-
 sidered afresh by a Committee of Experts. Five manufacturers, including
 the two petitioner in T.C .. Nos. 13 and 14 of 1992 and M/s. Roussel
 Pharmaceuticals India Ltd. had sent their representative tO put forward D
 their vii;ws in person, but apart from Mis Roussel Pharmaceuticals, none
 of the ~ther manufacturers presented any scientific paper or any fresh
 evidence in support of continued marketing of fixed dose wmbination of
 stroids for internal'use. The literature which was submitted by M/s. Roussel
 Pharmaceuticals India Ltd. had been earlier submitted by them on October
 16-17, 1987. The said material and other literature on the subject was E
 considered by the Experts Committee at the meeting held on June 6, 1989.
The Experts Committee have expressed the view that the literature did not
establish the rationality of administering corticosteroids with other drugs
in a fixed dose manner for the treatment of bronchial asthama and that the
published papers that were submitted by the manufacturers to justify the F
continued marketing of the said fixed dose combination do not establish
the necessity of using a combination of number of drugs in sub-the:t:apeutic
doses instead of using one drug in therapeutic concentration for achieving
the same clinical benefit. The Experts Committee also opined that the
interpretation of the results made by respective authors are not scientific.
According to the Experts Committee there is no scientific evidence to show G
that there is a therapeutic rationality of co-administering bronchodialtors,
corticosteroids and seductive in a single tablet under a fixed dose and that
on the other hand there were several adverse reactions of corticosteroids
when indiscriminately used. The Experts have, therefore, found that there
is no case for granting exemption for continued marketing of fixed dose H
                                                                                   .•
                                                                                   ~




    398                  SUPREME COURT REPORTS [1993) SUPP. 2 S.C.R.

A   combination of corticosteroids with other drugs for the treatment of
    Asthma.

          On behalf of the petitioners, scientific data in the form of published
  papers in the various medical journals have been filed to show that fixed
B dose combination of a corticosteriod and an anti-histamine is highly benefi-
  cial for the treatment of asthma. It has been submitted that the said studies
  reveal that the patient can obtain an equally effective treatment by con-
  suming half the quantity of steroid and thereby the consumption of steroid
  is kept to the minimum possible level and further the combination has
  well-recognised synergistic and potentiating properties and characteristics
c as a result of which the treatment is far more effective for these allergic
  disorders than if the two drugs were taken seperately. It has also been
  urged that as the consumption of steroid is sharply reduced, the expense
  involved in the treatment is also curtailed significantly. It has also been
  pointed out that fixed dose combinations of corticosteroids and anti-his-
D tamine or broncho-dilators are being marketed freely in a number of
  countries such as Germany, Japan, France, Switzerland, Austria etc. It has
   also been urged that where the patient has to take two different tablets
   together at the same time, it is always a serious problem to ensure that he
   takes both of them regularly, and as required and that the problem of
   patient compliance is all the more acute in a country where the level of
E illiteracy is very high, as in India. Similarly, on behalf of the respondents
   extracts from medical treatises and foreign medical journals have been filed
   to show that fixed dose combination of cortisteroids and anti-histamines is
   irrational because anti-histamines have no role to play in asthma manage-
   ment and that in respe'ct of bronchial asthma, the standard treatment is
F broncho-dilator and in cases of severe chronical asthma where broncho-
   dilator alone fails to give disired result corticosteroids may be resorted as
   a therapy but the dosage needs to be regulated carfefully. It has been
   submitted that at no stage fixed dose combinations of cortiosteroids with
   other drugs is recommended in the treatment of Asthma and that such
   combinations were either withdrawn or never introduced for marketing in
G the USA, UK etc. As regards the studies and reports that have been
   submitted by the petitioners, it has been pointed out that they are based
    on research done on animal models and no comparative study between
    corticosteroid alone and fixed dose combinations on the human beings
    have been shown and further that many of the studies are not authentic
H publications or are obsolete. It has been submitted that no standard boo'k
SYSTOPIC LABORATORIES (P.) LID. v. DR. P. GUPTA [AGRAWAL, J.] 399

or authentic medical journal speaks about fixed dose c_ombination of A
corticosteroids and other drugs in the management of asthma.

      Having cosidered the submissions made by the learned counsel for
the petitioners aµd the learned Additional Solicitor General in this regard,
we must express our inability to make an assessment about the relative
merits of the various studies and reports which have been placed before
                                                                               B
us. Such an evaluation is required to be done by the Central Government
while exercising its powers under Section 26A of the Act on the basis of
expert advice and the Act makes provision for obtaining such advice
through the Board and the DCC.
                                                                               c
        The learned counsel for the petitioners have urged that these studies
 and reports had been submitted on behalf of the petitioners and other
 manufacturers. before the Sub-Committee of the DCC as well as the
Experts Committee but there has been no proper consideration of the same
by the experts as well as the DCC and the Board. In this context, it has D
been submitted that no medical expert in the field of clinical medicine In
 the treatment of asthma was associated in the committees and such experts
alone could make a proper evaluation of the said studies. We find no
substance in this contention. We have pursued the minutes of the meetings
of the Board, the Sub-Committee of the DCC as well as the Experts
Committee. The minutes show that the material that was submitted on E
behalf of the manufacturers of the drugs in question was examined by the
memebers and it is not possible to hold that there has been no proper
consideration of the said material by the Experts Committee or the Sub-
committee of the DCC. The complaint that experts in clinical medicine
were not associated with the Committee does not appear to be justified. F
The minutes of the meetings of the experts to consider the views of the
affected manufacturers who represented against the proposed withdrawal
of certain formulations moving in the market which were held on Septem-
ber 8, 1987, October 16-17, 1987 and January 15-16, 1989 show that among
the members were included Dr. O.D. Gulati, Dean, CAM Medical College,
Karansad and Dr. J.P. Wali, Assistant Professor of Medicine, AIIMS, New G
Delhi. Dr. M. Durairaj, Consultant, Cardiologist, Director of Cardiology,
Poona Hospital & Research Centre, Pune was also member of the Sub-
committee and had attended the meeting held on January 15-16, 1988. It
cannot, therefore, be said that medical experts in clinical medicine were
not associated in the Experts Committee for evaluation of the material that H
    400                   SUPREME COURT REPORTS [1993] SUPP. 2 S.C.R.

A was furnished by the manufacturers.

         It has alsci been contended that in the meeting of experts held on
  September 8, 1987, the criteria/guidelines had been indicated for evaluation
  of each category of formulation and that in the said criteria/guidelines
B reference is made to comparative clinical trials with the formulation. It has
  been urged that no such clinical trials of fixed dose combinations of
  corticosteroids with anti-histamines or broncho-dialators were conducted
  prior to the issuance of the impugned notification dated November 3, 1988
  and in the absence of such clinical trials, the Central Government could
  not have been satisfied that long term use of fixed dose combinations of
C corticosteroids with any other drug for internal use for treatment of asthma
  do not have therapic justification. It is no doubt true that at the meeting
  of experts held on September 8, 1987 certain criteria/guidelines wer indi-
  cated and one of the said criteria/guidelines refers to adequate controlled
  comparative clinical trial with the formulation. But those criteria/guidelines
D were indicated in respect of 12 types of formulations which were under
  consideration Combinations of corticosteroids with other drugs for sys-
  tematic use for the treatment of bronchoialasthma was one of those for-
  mulations. With regard to fixed dose combination of chloramphenicol
  streptomycin and fixed dose combination of steroids with bronchodilators
  for systematic use, the minutes of the meeting of the Sub-Committee held
E on January 15-16, 1988, record that "the experts had opined that little will
  be achieved by conducting clinical trials on these categor~es and reiterated
  its earlier stand of recommending withdrawal of fixed dose combination of
  chloramphenicol with streptomycin and fixed dose combination of steroids
  with bronchodilators for systematic use". This ·would show that the experts
F did not consider it necessary to conduct clinical trials in respect of fixed
  dose combination of steroids with bronchodilators for systematic use. The
  petitioners and other manufacturers, it they so desired, could have sub-
  mitted fresh material based on clinical trials conducted during the period
  subsequent to notification dated July 23, 1983 in justification of their case
  before the experts. They did not, however, do so and the only produced
G material which was anterior to the notification dated July 23, 1983. As to
  whether clinical trials should have been conducted or not was primarily for
  the experts to decide and if the experts felt that the respect of the drugs
  in question such clinical trials were not necessary, it is not possible to hold
  that there has been no proper evaluation of the material that was submitted
H by the manufacturers before the Experts Committee.
SYSTOPICLABORATORIES (P.) LTD. v. DR. P. GUPTA(AGRAWAL,J.] 401

       Another contention that has been advanced on behalf of the A
petitioners was that under impugned notification dated November 3, 1988,
there is complete prohibition of the manufacture and sale of fixed dose
combination of corticosteroids with any other drug for internal use and that
such a prohibition unreasonably restricts the right of the petitioners to
carry on their trade guaranteed under Article 19(1)(g) of the Constitution.
The submission is that in order that the said restriction could be regarded
                                                                             B
as a reasonable restriction it was necessary for the authorities to consider
whether a less drastic course could be adopted, namely, permitting
manufacture and sale of such drugs with a warning about its use. Reliance,
in this regard, has been placed on the observations of this Court in Mohd.
Farnk v. State of Madhya Pradesh and others, [1970] 1SCR156. We do not           c
find any merit in this contention.

       In State of Madras v. V.G. Row, [1952] SCR 597, this Court, while
emphasising that "no abstract standard or general pattern of reasonable-
ness can be laid down as applicable in all cases" has indicated the following
criteria for examining the reaspnabless of the restrictions under Article 19: D

        "The nature of the right alleged to have been infrigned, the under-
        lying purpose of the restrictions imposed, the extent and urgency
        of the evil sought to be remedied thereby, the disproportion of the
        imposition, the prevailing conditions at the time, ......... " (p.607)   E

       In Narendra Kumar and Others v. The Union of India and Others,
(1960] 2 SCR 375, this Court has construed the term 'restriction' in Article
19 to include prohibition and has held that the reasonableness of such a
restriction has to be considered "in the background of the facts and
circumstances under which the order was made, taking into account the F
nature of the evil that was sought to be remedied by such law, the ratio of
the harm caused to individual citizens by the proposed remedy, to the
beneficial effect reasonably expected to result to the general public", and
"whether the restraint caused by the law was more than what ,was necessary
in the interests of the general public" (pp.387-388)                         G

     In Mohd. Farnk v. State of Madhya Pradesh (supra), it has been
observed :

        "The Court must in considering the validity of the impugned law
        imposing a prohibition on the carrying on of a business or profes- H
    402                   SUPREME COURT REPORTS [1993) SUPP. 2 S.C.R.

A            sion, attempt an evaluation of its direct and immediate impact
             upon the fundamental rights of the citizens affected thereby and
             the larger public interest sought to be ensured in the light of the
             object sought to be achieved, the necessity to restrict the citizen's
             freedom, the inherent pernicious nature of the act prohibited or
             its capacity or tendency to be harmful to the general public, the
B            possibility of achieving the object by imposing a less drastic
             restraint, and in the absence of exceptional situations such as the
             prevalence of a state of emergency - national or local- or the
             necessity to maintain essential supplies, or the necessity to stop
             activities inherently dangerous, the existence of a machinery to
c            satisfy the administrative authority that no case for imposing the
             restriction is made out or that a less drastic restriction may ensure
             the object intended to be achieved". (p. 161)              ·


         If the present case is considered in the light of the aforesaid tests, it
D cannot be said that the impugned notification prohibiting the manufacture
  and sale of the drug in question suffers from the vice of unreasonableness.
  In taking this step the Central Government appears to have moved in a
  cautious manner. In the earlier notification dated July 23, 1983, whereby
  manufacture and sale of a number of drugs, including fixed dose combina-
E tions of certain drugs, was prohibited an exception was made in respect of
  fixed dose combinations of corticosteroids with other drugs for the treat-
  ment of asthma. At· that time also the DCC had expressed the view that
  fixed dose combinations of corticosteroids with other drugs were con-
  sidered harmful for the reason that (i) the adrenal suppression accompany-
  ing steroid therapy leads to symptoms and signs of adrenal insufficiency, if
F the steroid is abruptly withdrawn; and (ii) it is difficult to titrate the dose
   of a steroid when it is present in fixed dose combinations v,.ith other drugs.
   The DCC had experesed the view that fixed dose combinations of cor-
  'ticosteroids with other drugs are not justifiable as indiscriminate use of
   corticosteroids can porduced serious side effects and in certain clinical
G conditions where adirninistration of steroids is considered necessary, the
   drug can be prescibed sep~rately. The Board, however, felt that so far as
   combination of steroids with other drugs for treatment of asthma are
   concerned, there was need for examining the matter in further details and
   getting wider opinion in the matter and therefore, the Board recommended
H that such combination may continue for the present. Keeping in view the
SYSTOPIC LABORATORIES (P.) L1D. v. DR. P. GUPTA [AGRAWAL, J.) 403

 said recommendation of the Board the Central Government excluded A
 combination of steroids with other drugs for the treatment of Asthma from
 the ban imposed by notification dated July 23, 1983. The matter 'was
 thereafter examined in detail by the Sub-Committee of the DCC as well as
the Experts Committee in 1987-88 and the representatives of the manufac-
 turers were given adequate opportunity of producing material in support B
of continued marketing of the said drugs and they were also personally
heard. After taking into consideration all the relevant data that were made
available, the Sub-Committee of Experts for weeding out harmful/irrational
formulations expressed the same view as was held by DCC earlier and they
opined that fixed dose combinations of corticosteroids with any other drug
should not be allowed because in the recommended upper dosage limit the
                                                                         c
daily dose of corticosteroid often exceeds safe pharmacological limit for
adrenocortical suppression and that the combinations do not permit titra-
 tion of the steroid doses which is often required in practice or the ad-
ministration of the minimum daily dose once a day so as to avoid
 adrenocortical suppression. The experts also ROinted out that there is D
hardly any authentic reference to support that f~ed dose combination of
corticosteroids with bronchodilators or anti-histanines are recommended
in the treatment of Asthma. Agreeing with the said view the Board recom-
mended that the fixed dose combinations of corticosteroids with other
drugs for use in Asthma should be banned because asthma therapy is a E
long term therapy and corticosteroids in dosage when administered for
longer periods are reported to cause more harm than good to the patients.
While examining the reasonableness of the prohibition against manufacture
and sale of the said drugs the harmful potentialities of the drugs have to
be considered in the context of the conditions as prevalent in the country F
where, on account of illiteracy, people are not aware of the ill effects of
the drugs available in the market and are often misled and misguided by
quacks and inexperienced doctors. The less drastic course of permitting
manufacture and sale of the drugs with a warning about its use, suggested
by the learned counsel for the petitioner, would, in our opinion, not be
adequate to protect the general public from the harmful consequence. It G
is, therfore, not possible to hold that the prohibition which has been
imposed by the impugned notification on the manufacture and sale of the
drug in question imposes an unreasonable restriction so as to be violative
of the right guaranteed under Article 19(1)(g) of the Constitution.
                                                                         H
    404                    SUPREME COURT REPORTS (1993] SUPP. 2 S.C.R.

A         The learned Additional Solicitor General has pointed out that in view
    of the observations made by this Court in its order dated January 6, 1992
    in SLP(C) No. 1588 of 1989, the matter is being considered by the Tech-
    nical Advisory Board in the light of the fresh material that has been placed
    before the Board. Having regard to the aforesaid observations in the order
B   dated January 6, 1992, the petitioners as well as other manufacturers who
    have filed writ petitions in the High Court and whose writ petitions are
    pending in the High Court can also approach the Board and produce any
    fresh material in support of thefr claim for revocation of the ban on
    manufacture and sale of fixed dose combination of corticosteroids with any
    drug for internal use for treatment of Asthma. The Board, while consider-
c   ing the matter would take into account the said materi<tl which is placed
    before it. The petitioners and other manufacturers desirous of availing this
    opportunity of reconsideration of the matter may submit the material in
    pursuance of this order before the Board within a period of one month.

D           It has been urged on behalf of the petitioners that on December 16,
    1922, the Court had pass!fl an interim order whereby the operation of the
    judgment and the order of the Punjab and Haryana High Court dated June
    3, 1992 was stayed for a period of two months and the petitioners were
    permitted, if they so desired, to manufacture the drug subject to the
E condition that the quantum of their monthly production could not exceed
    the monthly average of their earlier production calculated at the average
    of 12 months immediately preceding November 3, 1988. By order dated
    February 4, 1993, in the order dated December 16/17, 1992, the date 3rd
    November, 1988 was substituted by the date 3rd June, 1992. By order dated
F . April 22, 1993 the period of two months was extended for a futher period
    of four months or till the final disposal and the matters whichever is earlier.
    On behalf of the petitioners, it has been urged that in pursuance of the
    said order drugs have been manufactured by the petitioners and that the
    prohibition against sale should be deferred till the existing stocks are sold.
    Since interim directions were limited to production for a short period only
G on the basis of the average monthly production, there is no reason to
     <1_ssume that large stocks of drugs are lying with the petitioners. In the
    circumstances, we do not consider it appropriate to give any direction
     regarding permitting the petitioners to sell the existing stocks of the drugs.

H          In the result, the appeals, the special leave petitions as well as the
SYSTOPICLABORATORIES(P.)LTD. v. DR.P.GUPTA[AGRAWAL,J.]405

Transferred cases and writ petition are dismissed. The judgment of the A
High Court of Punjab and Haryana, under appeal, is affirmed subject to
the direction that it would be permissible for the petitioners in these cases
and other manufacturers whose writ petitions are pending in the High
Courts to approach the Board and place before the Board any fresh
material in support of their claim within a period of one month and any B
such representation as well as the material produced in support thereof
shall be considered by the Board along with representation submitted in
pursuance of the direction given by the Court in order dated January 6,
1992 in SLP(C) No.15382of1991. This shall be done within three months
of the filing of the representations. No order as to costs.
                                                                           c
G.N.                                                  Matters dismissed.