Eye Watch On Pharma Industry-II

• What is COPP ?

COPP is Certificate of a Pharmaceutical Product. It is an export certificates for unapproved products, that are not authorized for sale in country, which may be legally exported to foreign governments. It is recom mended by W HO.

• How many types of application for revision or renewal of Certificate of Suitability ?

Simple Notification
Multiple Notifications (max 3) Simple minor revision
Multiple minor revisions (max 3)
Simple major revision
Multiple major revisions (1 major, max 3 in total) Consolidated revision (more than 3 changes) Quinquennial renewal
Evaluation of sterilisation data

Notifications :
The determination of validity of a notification is com pleted within 2 weeks after receipt of a request.
Then either an acknowl edgement of a valid notification is sent or a revised certificate is granted if necessary.
An application for multiple simultaneous notifications is possible under conditions: - maximum 3 changes.

Minor changes :
T 0 (within 5 days after receipt of the request): a letter of acknowl edgement of receipt is sent to the applicant.
T 30 days: either the request is approved and a revised certificate is granted. or
A letter of request for additional information is sent (clock-stop).
If clock-stop: the applicant is requested to subm it a reply within 30 days.
Failure to subm it a reply in time will lead to the rejection of the request for revision. Again new T0 and new T 30 day’s process will start.

Major changes :
T 0 (within 5 days after receipt): a letter of acknowl edgement of receipt is sent to the applicant.
T 90 days: either the request is approved and a revised certificate is granted. or
A letter of request for additional information is sent (clock-stop).
If clock-stop: the applicant is requested to subm it a reply within 30 days.
Failure to subm it a reply in time will lead to the rejection of the request for revision.
Again new T0 and new T 30 day’s (except TSE certificates: 90 days) process will start.

Quinquennial renewal :
The holder of the certificate should apply for the renewal of their certificate about 6 months prior to expiry date. T0 (within 5 days after receipt): a letter of acknowl edgement of receipt is sent to the applicant.
T 120 days: either approval and a renewed certificate is sent.
or
A letter of request for additional information is sent (clock-stop).
If clock-stop: the applicant is requested to subm it a reply within 30 days.
Failure to subm it a reply in time will lead to the rejection of the request for revision.
Again new T0 and new T 30 day’s (except TSE certificates: 90 days) process will start.

Monographs revisions :
W hen a revised monograph is published, a letter is sent to the relevant holders of to update their dossier. The holder is requested to subm it the data within 90 days.
T0: At receipt of the data, start of evaluation (no letter from EDQM) T120 days: sending of an acknowl edgement of valid data.
or
A letter of request for additional information (clock-stop).
If clock-stop: the applicant is requested to subm it a reply within 30 days.
Failure to subm it a reply in time will lead to the rejection of the request for revision. Again new T0 and new T 30 day’s process will start.

• What is the Structure and Content of Drug Subm issions In CTD Format ?

Common Technical Docum ent (CTD) is updated and harmonized format for Drug Master File (DMF) for registration
for pharmaceuticals for human use. It is accepted by most of the regulatory agencies. Modules suggested by ICH as follows :

Module 1: Administrative Information and Prescribing Information
Module 2: Common Technical Docum ent Summaries
Module 3: Quality
Module 4: Nonclinical Study Reports
Module 5: Clinical Study Reports

• What are the topic to be covered in CTD subm ission for Drug Substance ?

Module 3.2 : Body of data

1. General Information
2 Manufacture
3 Characterisation
4 Control of the Drug Substance
5 Reference Standards or Materials
6 Container Closure System
7 Stability
1.1 Nomenclature
1.2 Structure
1.3 General Properties
2.1 Manufacturer(s)
2.2 Description of Manufacturing Process and Process Controls
2.3 Control of Materials
2.4 Controls of Critical Steps and Intermediates
2.5 Process Validation and/or Evaluation
2.6 Manufacturing Process Development
3.1 Elucidation of Structure and other Characteristics
3.2 Impurities
4.1 Specification
4.2 Analytical Procedures
4.3 Validation of Analytical Procedures
4.4 Batch Analyses
4.5 Justification of Specification
7.1 Stability Summary and Conclusions
7.2 Post-approval Stability Protocol and Stability Commitment
7.3 Stability Data
Module 2.3 : Quality Overall Summary

• guideline is supporting to address the changes in USA ?

W e can address the changes of APIs as per BACPAC [Bulk Actives Post Approval Changes]. But it was withdrawn by
USFDA on 06.01.2006. No other guideline is available from USFDA as on date.

W e can address the changes of formulation related issues as per SUPAC [Scale Up & Post Approval Changes].

• Which guideline is supporting to address the changes of APIs in Europe ?

As per Guideline of request for revision or renewal of Certificate of Suitability.

• How to address the variation in EU on Medicines & Health Products ?

• What is DCGI and NPPA ?

DCGI : Drugs Controller General of India.

NPPA : National Pharmaceutical Pricing Authority [Drug Price Regulator]

• What is the general procedure for USFDA Audit ?

As per FDA Form 2438 [Effective from February 2006] . There are two basic types of inspections :
1. Surveillance 2. Compliance

Surveillance inspections are conduct ed on a routine basis to satisfy FDA’s responsibilities to inspect drug- manufacturing facilities.

Compliance inspections are conduct ed in response to violative surveillance inspections and when a need arises to inspect a facility for-cause.

This program follows the approach in the main com pliance program.

There are two alternate approaches to inspecting a facility to satisfy FDA inspection obligations :

1. Full Inspection 2. Abbreviated Inspection

A general scheme of systems for auditing the manufacture of API consists of the following:

1. Quality System 2. Facilities and Equipment System
3. Materials System 4. Production System
5. Packagi ng and Labeling System 6. Laboratory Control System

• What is NDC numbering system ?

National Drug Code is a unique 10-digit, 3-segment number.

1st segment is the Labeller Code. It is assigned by the FDA.

2nd segment is the Product Code. It is to be assigned by the firm with respect to identifies a specific strength, dosage form, and formulation for a particular firm.

3rd segment is the Package Code. It is also to be assigned by the firm to identifies package sizes and types. The NDC will be in one of the following configurations: 4-4-2, 5-3-2, or 5-4-1.
Because of a conflict with the HIPAA standard of an 11 digit NDC, many programs will pad the product code or package code segments of the NDC with a leading zero instead of the asterisk. Since a zero can be a valid digit in the NDC, this can lead to confusion when trying to reconstitute the NDC back to its FDA standard.

Example: 12345-0678-09 (11 digits) could be 12345-678-09 or 12345-0678-9 depending on the firm's configuration.

By storing the segments as character data and using the * as place holders we eliminate the confusion.

In the example, FDA stores the segments as 12345-*678-09 for 5-3-2configuration or 12345-0678-*9 for 5-4-1
configuration.

• What is SMF ?

SMF (Site Master File) is a docum ent prepared by the manufacturer containing specific and factual Good Manufacturing Practice information about the production and/or control of pharmaceutical manufacturing operations carried out at the named site.

SMF should be concisely written in English and as far as possible no exceed 25-30 A4 sheets. SMF should have edition number and effective date.

W e can make the SMF as per guidelines of Schedule-M, PIC/S, HAS, MCC, ect.