The document discusses the roles and responsibilities of chemistry, manufacturing, and controls (CMC) regulatory affairs professionals. CMC ensures that pharmaceutical products are manufactured according to good manufacturing practices and that facilities meet regulatory standards. CMC regulatory affairs professionals work with various teams to provide CMC strategy, submit required information to regulatory agencies for approvals, and make submissions for any post-approval changes or studies. They act as responsible agents and certify that submissions meet all requirements.

1. CMC[Chemistry,
manufacturing,Control]&
Post Approval Regulatory
affairs
Presented by- Sakshi Rajendra Sonawane
M pharm.first year
Dept.of Pharmaceutics

2. INTRODUCTION-
 CMC stands for Chemistry, Manufacturing, and controls.
 It plays a pivotal role in the development, licensure,manufacturing and ongoing
marketing of pharmaceuticalproducts.
 CMC team has a similar function to the product development team, focused on
the manufacturing process development, registration, manufacturing facility &
siteinspections.
 It ensures compliance to cGMP, GLP & Clinical practices.
 It also audit compliance & readiness for regulatory inspections of the laboratory
clinical & manufacturing facilities & information technologies.
 The required content and format of the CMC section of various application types
are described in guidance documents from both the "International Conference On
harmonisation" (ICH)

3.  CMC is relatively small section (approx. 15-20%) of a typical new drug
application(NDA), but it often becomes a reason for delay in the approval of
NDA/Biologics licensing application(BLAs).
 For ANDA CMC section is significant(around 80-90%).It is important section in
post approval life cyclemanagement of the products. It should be noted that
CMC section is made up of threedistinctly different but overlapping
disciplines/sciences which are:-
1.Synthetic/ Fermentation Chemistry
2.Analytical Chemistry
3.Formulation Chemistry.

4. CMC Regulatory Affairs:
 To conduct clinical investigations and market pharmaceutical products,
pharmaceutical companies are legally required to obtain and maintain
regulatory approvals.
 The government regulatory agencies typically involved in the approval
 process are:The Food and Drug Administration(FDA); European Medicines
Agency(EMA);Japanese Pharmaceuticals and Medical Devices Agency (PMDA),
etc.
 CMC(RA) is a specific area with in RA that has the ultimate responsibility for
providing CMC regulatory leadership and strategy required to achieve
regulatory approvals.
 As a strategic function CMC RA collaborates closely with multiple
scientific,technical, quality, and commercial areas within a company or with
external contract manufacturing organisations (CMOS).
 Information regarding CMC for drugs is an important and detailed section in a
dossier to support clinical studies &marketing applications. This information
must be updated throughout drug’s lifecycle

5. CMC REGULATIONS:
 21 CFR 312.23(a)(7)(i) –
 As appropriate for the particular investigations covered by the IND, a section
describing the composition, manufacture, and control of the drug substance
and the drug product sufficientpurity CMC information to assure the proper
identification, quality, purity and strength of the investigational drug

6. OBJECTIVE OF CMC
 To assure that the drug sold to the public will have quality attributes similar
to those of the drug demonstrated to be safe and effective.
 To assure that the quality of the drug meets appropriate standards and is
consistent.
 To assure that the drug you are using is the drug described on the label
 provides the strategy and knowledge needed to ensure that CMC practices are
carried out in accordance with the requirements of regulatory bodies, such as
the FDA (US Food and Drug Administration) and EMA (European Medicines
Agency).
 providing the FDA with scientific data characterizing the therapeutic
molecule, its stability and formulation, the manufacturing process, and how
the manufacturer is planning to ensure consistency and control of the product
throughout the product life cycle.

8.  CMC is one of the links connecting Clinical Batches to commercial batches
Clinical
Batches (
safety and
effectivene
ss study)
Pilot
Batches
CMC
informati
on
Engineering
Batches Scale-up
from pilot to
commercial
Process Validation Batches
Implementation of
commercial
manufacturing processes
Commercial Batches
Product marketed to
consumers

9.  Example: CMC regulatory submission may contain information
 associated with API and the finished dosage form,:including.
 Names and location of manufacturing and testing sites .
 Characterization of the API and composition of the dosage form .
 Raw materials used to manufacture the API and finished dosage form .
 Description of the product and process development.
 Description of the manufacturing process.
 Analytical methods and specifications used for testing and release of raw
materials, in-process controls, container and closure system,API and dosage
form.
 Quality testing, bio equivalence testing .
 Release and stability testing data for both API and the dosage form

10. Post approval Regulatory Affairs:
 The FDA may require a post-approval study at the time of approval
of a Premarket Approval (PMA), Humanitarian Device Exemption
(HDE), or product development protocol (PDP) application to help
assure continued safety and effectiveness (or continued probable
benefit, in the case of an HDE) of the approved drug product of
medical device.
 A sponsor’s failure to comply with any post-approval requirement
may be grounds for withdrawing approval i.e. whether the post
approval study will be terminated or revised/replaced.
 The safety surveillance is designed to detect any rare or long-term adverse
effect s over the much larger population and longer timeperiod.
 Harmful effects shown in this trial may result in drug ban or restricted in
certain usages.

11. Post approval study:
• Drug-drug interaction
• Drug-food interaction
• Drug- herbal interaction
• Pharmacoeconomic
• Expanded efficinency/safety
• Additional indication
• Strategies for minimization
of adverse effect.
• Strategies for dose
indivisuilization
• Optimization of surrogate
lab test
• Special populations
• New formulation

12. Submission Type
 An application must provide specific information to access the effect of the
quality, purity and potency of a drug product.
 REPORTING CATEGORIES-
1. MAJOR CHANGE- substantial potential
2. MODERATE CHANGE- moderate potential
3. MINOR CHANGE- minimal potential

13.  When to submit post approval study protocol-
 Ideally, the final protocol for a post-approval study and the schedule for study
completion are based on agreements reached between FDA and the sponsor
during the PMA review process prior to approval of the PMA, accordingly it is
recommended you submit a proposed post-approval study protocol or, at
minimum, post-approval study plans, in the original PMA submission
 How to submit changes-
 If you wish to propose a change to an approved post-approval study protocol,
it is recommended you submit a PMA supplement clearly labeled as a post-
approval study protocol, for FDA review and approval. If multiple protocols
are to be revised, we recommended each be submitted as a separate PMA
supplement.

14.  CMC regulatory affairs is concerned with the technical characteristics of a
drug molecule and the dosage form used for itsadministration.
 Typical list of CMC information required for evaluation. CMC Database or a
New Drug Application : Drug Substance – Physicochemical properties,
synthetic process, controls for starting materials,reagents,etc.,process
control for intermediates, specifications and analytical methods, list of
impurities, stability and life to retest.
• Drug Product – Components an composition,
manufacturers, method of manufacturing and packaging,
specifications and analytical methods, stability information. In
the preapproval phase of the product life cycle, CMC
information is initially provided to FDA through and IND
application. Depending on the outcome of clinical trials
conducted under the IND, an NDA may be filed with an
additional level of CMC information.
• In the post approval phase, the regulatory affairs professional
• is responsible for managing changes to these conditions.

15. Comparison of CMC Regulatory
Environments :
Preapproval Postapporval
Type of submissions- Supplemental NDAs
Annual Reports
CMC Commitments
Internal customer
R & D (Research and
Development)
Manufacturing
Manufacturing
Customer priority
Supporting INDs & NDAs Manufacturing product
Timelines Months and years Weeks and months
Format of submission Well defined Less defined
Reference base of Being developed as part Approval Condition In
INDs and NDAs
(investigational new
drug application & new
drug application)

16.  In order to make CMC changes to the conditions of approval in the NDA, the
drug manufacturer must file the changes with FDA through one of the various
types of post approval submissions.
 Prior to 1997, the regulation governing CMC changes to an approved NDA was
21 CFR 314.70 (Supplements and other changes to an approved application).
This statute was established in February 1995 as part of a comprehensive
effort to improve the NDA and post approval application process.
 There are 3 reporting categories For post approval changes:
(1) Prior approval suppliment
(2) Changes being affected (CBE) Supplement, and
(3) Annual report
● CMC Postapproval Regulatory Submissions : Prior approval suppliment : A
prior approval suppliment is required for a CMC changes that has a
substaintial(major) potential to have an adverse
effect on the identity, strength, quality, purity, or
potency of the product as they may relate to its safety
and effectiveness.

17. The CMC Postapproval Regulatory Professional As The "Responsible
Agents"
 The CMC Postapproval Regulatory Professional As The "Responsible Agents"All
regulatory submission are accompanied by FDA from 356h singed by the
regulatory affairs professional acting as a "responsible agent "for the drug
manufacturer. The form includes a number of certification statements that
define the scope of responsibility associated with this role. The role of acting
as a responsible agent is what differentiates the CMC regulatory affairs
professional from other functional groups involved with compiling and
submiting postapproval application.

18. Thanking You!