Roche Advisory Committee
This Addendum Report is being submitted on behalf of all
the FDA approved generic manufacturers and distributors of Isotretinoin
Capsules to provide comments on the
Risk Management Program
Mylan/Bertek – Distributor
Ranbaxy Pharmaceuticals, Inc.
1System to Prevent Isotretinoin-Related
2Isotretinoin Medication Program Alerting you to the Risks of Teratogenicity.
3Adverse Event Learning and Education Regarding Teratogenicity.
part of the FDA requirements for the approval of an ANDA,
the generic product must have the same or equivalent labeling and risk
management program as the innovator product.
Therefore, all the generic products have risk management
programs that are the same as Roche’s S.M.A.R.T. program.
called a meeting on December 10, 2003 of all manufacturers and distributors of
isotretinoin capsules to discuss the Agency’s findings and concerns with the
current isotretinoin risk management program for the prevention of pregnancy. FDA informed the companies of the planned
joint meeting of the Drug Safety and Risk Management Advisory Committee and the
Dermatologic and Ophthalmic Drugs Advisory Committee on February 26 and 27,
2004 to discuss the effectiveness of the isotretinoin risk management program for
the prevention of fetal exposure to Accutane and its generic equivalents, and
consider whether changes to this isotretinoin risk management program would be
appropriate. During the December 10th
meeting, FDA suggested that, ideally, the companies should work together to
develop a consensus proposal to enhance the current risk management program.
They also strongly suggested that any proposal contain a plan for a single
repository or registry for data collection to permit meaningful analysis of
data (Note- there are currently two separate voluntary
registries f or female
patients. Roche maintains one registry, and
the Slone Institute at Boston University maintains the other registry under contract
by the generic companies.) FDA informed the companies that an industry proposal
was due to the Agency on January 26, 2004 to assure adequate lead-time for FDA
review and dissemination to Advisory Committee members. This proposal would then be presented at the
Advisory Committee Meeting in February.
The Agency primarily focused on the fact that the absolute number of pregnancies reported the year prior to the initiation of the current S.M.A.R.T. Program and those reported during the first year after its full implementation were about the same. Because there is no way to determine the actual rate of pregnancies or to know how completely pregnancies were reported, it is not possible to determine whether the implementation of the S.M.A.R.T. risk management program resulted in increased pregnancy reporting or that the program failed to decrease the number of fetal exposures. However, all of the generic companies and Roche as a way
believe that program
enhancements to the current risk management program would be beneficial in
reducing fetal exposure.
that there was very little time for all the companies, the generics and Roche,
to reach consensus, immediately following the FDA meeting, the companies agreed
· Mandatory prescriber registration.
· Mandatory registration of all female patients receiving a prescription for isotretinoin.
· Prescriber attestation of patient education/qualification in the system for each isotretinoin prescription.
· Mandatory reporting to the system of the results of a pregnancy test (for female patients of childbearing potential) conducted by an accredited laboratory within an appropriate time frame.
· Mandatory use of a Qualification Sticker on each isotretinoin prescription (Note- sticker would designate male or female patient).
· Dispensing of isotretinoin to female patients only if a current negative pregnancy test (for females of child bearing potential) is recorded in the system and the system provides an appropriate authorization number prior to dispensing or for a male patient if the appropriate authorization sticker is affixed to the prescription.
· Requires the pharmacist to access the registry system to confirm an authorization to dispense the drug for each and every prescription for a female patient
· Mandatory identification of product.
· Centralized mechanism for reporting and follow-up of pregnancies.
January 16, 2004, Roche, on behalf of all of the companies, sent a draft
process flow diagram (See Attachment 2) and a high level description containing
the sixteen consensus points for the proposed pregnancy risk management program
(See Attachment 1) to the Agency. The
companies and FDA participated in a teleconference on January 23, 2004 to
discuss the Agency’s comments on the consensus proposal. The primary comments from the Agency on the
concerned three areas:
(l) Registration of male patients in addition to female patients versus only female patients;
(2) Patient interaction with the educational and risk management evaluation component of the program; and
(3) A firmer link between the registry and the pharmacist - perhaps through pharmacy registration.
following the FDA/Company teleconference, the companies met via teleconference
to discuss the Agency comments and determine next steps.
All companies continue
to support the 16-point consensus proposal as submitted to FDA on Jan. 23,
2004; however, there was not consensus on how to address the three issues the FDA raised during the
teleconference. Since the
briefing document was due that day, there was inadequate time
to resolve the differences
between Roche and the generic companies on the approach to address the Agency’s
comments. Therefore, Roche decided to submit a
separate briefing document that included the original sixteen-point consensus
proposal but also added additional points to address the three issues raised in
the FDA teleconference.
January16January 23, 2004
The generic companies
firmly agree that enhancements to the current isotretinoin risk management
program are appropriate. We
continue to support the overall proposal as submitted in the Roche briefing
document with the exceptions of the three issues described above. D ue to the limited
meeting time available to the companies between the Jan. 23, 2004 FDA
teleconference and the Jan. 26, 2004 submission date, the companies were not
able to adequately discuss the proposals to address the Agency’s comments on our original consensus sixteen-point
proposal in order to reach a consensus. With respect to three issues raised
during the FDA/Company teleconference, the
generic companies have taken them under advisement and
request that they be addressed at the advisory meeting in the context of the
changes proposed to the
isotretinoin risk management program.