Know Your Pharma Industry(Part-I)

(a). DMF:
- Drug Master file.
Definition:- It is the document submitted voluntarily to regulatory authorities containing confidential information about process and facilities.
Requirements for DMF filing:-
1. Process: - a. Batch production Records b. In process controls c.
Intermediates
2. Facility address:
3. Production facilities: - a. Area b. Capacity.
4. Production Equipment:- a. GLR’S b. SSR’S c. Centrifuges d. Nutch, candy, leaf & Micro filters e. Driers like conevaccum drier tray drier f. Sifting equipments & bantom milling equipments etc.
5. Quality control: - a. In process control, b. Validation c. Specification and S T P’s of starting materials (Raw materials) intermediates, finished products etc.
6. Drug Description:- a. Chemical Abstract studies number b. Molecular formula c. Molecule structure d. Structural elucidation report etc.
7. Impurity profile:- a. process impurities b. Degradation impurities c. By products.
8. Analytical method validation:- HPLC, GC Analysis as per symphony.
9. Certificate of Analysis (COA) of reference standard, working standard and final product & their NMR & Mass.
10. List of major lab equipments :- a. Glass ware b. Stirrers c. Regulators d. Balances e. UV chambers f. Oven g. Autoclave h. MR apparatus i. Buchi Rotavapour systems k. high vacuum pumps & Diaphram pump etc.
11. Ware house facility Description:- Storage conditions
12. Organization chart:- Key persons Information
13. Production flow sheet or plant layout:-
14. Scheme process flow sheet & process Description:- Commercially availability of starting materials to total BPR.
15. Complaints filing:
16. Environment Assessment: SH&E package.
17. Annexcires BPR’s & Product labels:-
DMF Submission in Europe contains two parts.
Open part
Closed part
1. Open part:- (or) Applicant part:-

Nomenclature , structure and general properties like MR, solubility, Description & polymorphism.
Synthetic route chemical pathway.
Structural elucidation.
Impurity write up & impurity profile
Stability write up.
Control of active substance, final product specifications, COA and MOA, validation.
Reference standard : preparation & COA.
Container close system:- Closing & reading spec’s STP’s COA.
Manufacture:- Address.
2. Closed part or Aim restricted part:- API manufacture.
Address
Process validation or evaluation, process description & process control.
Specifications & STP’s of raw materials, intermediates, in process control & finished products.
DMF filing should be done by regulatory affairs.
DMF filing is compulsory for USFDA.
Regulatory affairs:- Responsibilities:
1. DMF filing \
2. Customer requirement
3. External affairs
4. As per regulatory requirements US, Europe & ROW
Drug master file is a reference source that provides confidential information not available to drug product manufacturers about the specifications, process and components used in the manufacturing, processing & packaging of drug meant for human use.
The submission of drug master file is not required by law & FDA regulation. A DMF is submitted slowly at the discretion of the holder. The information constricted in the DMF may be used to support on ‘IND, NDA & ANDA or another DMF or amendments and supplements to any of these.
A DMF is not a substitute for an IND, NDA, ANDA. It is not approved or disapproved. Technical contents of a DMF are revived only in connection with the review of an IND, NDA & ANDA.
Ib
US FDA Inspections.
Drug Inspections
Drug firms
New drugs
Manufacture of API and finished
Investigational new drugs
Product
Antibioties
Contract packages
Prescription drugs
Contract laboratories
Non perception drugs etc
Distributors, brokers & ware houses.
Types of Inspections: 1. GMP inspections 2. Pre-Approval inspections 3. Post –approval inspections 4. Other consumer complaints, recalls, drug quality reporting system etc.
Purpose of Inspections:
1. To ensure that production and control procedures include a reasonable predictions to ensure the identity, strength, quality & purity of the finished product.
2. To determinate and evaluate them, adherence to CGMP,s
Preparation and managing as USFDA inspection :-
Preparation:-
Conduct internal quality audits : 1 identifying potential problems 2 recommended connective actions 3 implements appropriate actions 4 conduct follow up audits.
Source of internal audits information: 1 Annual product reviews 2 batch failures 3 reprocess batches 4 returned goods 5 complaints related to product quality 6 recalled goods 7 stability failures.
FDA inspection Involves: 1. Direct observations of buildings, equipments, production, processes employer practices, records etc.
2. Systems approach like validation processes, equipment cleaning validations production and process controls established SOP’s documented activities method validations instrument handling and out of specification, master batch cards, complaint handling etc.
Internal audits: - Compare actual operations with DMF/NDA/ANDA and supplement commitments, commitments, company SOP’s FD&C Act requirement, CGMP requirements, FDA policy & guidelines etc.
Managing an FDA inspections:- 1. Don’t panic & be honest while accompanying with FDA auditor, 2. Select appropriate person, note taken technical experts to provide information and discuss records and procedures. 3. Responding to FDA auditor’s questions, If you don’t understand the question, ask for clarification & then answer. 4. Document retrieval for FDA inspections should be prompt & accurate. 5. Persons with authority to promise or make corrective actions are present.
What is FDA-483:- It is a written document of inspectional observations of FDA investigator during an inspection of a company.
Purpose of FDA-483:- 1. To assist firms inspected in complying with the laws and regulations entered for the FDA. 2. To provide notification to top management of significant findings. 3. All CGMP deficiencies will be reported on FDA-483.
Holding and Distribution:- 1. Ware housing procedures 2. FIFO system to be followed 3. There shall be a system to facilitate product recall 4. Storage of drug product under appropriate conditions.
Laboratory confronts: 1. Establishment, specifications, standards & sampling plans and other laboratory mechanisms. 2. All procedures &n specifications must be scientifically sound. 3. Review and approval of procedures by quality unit. 4. Deviations from established systems shall be recorded & justified. 5. Established procedures and schedules for all laboratory instruments. 6. Analytical methods shall be validated. 7. Out of specifications shall be recorded. 8. Every bath to be released after meeting the established specifications.
Stability testing: 1. Stability studies shall be used in determining appropriate storage conditions and expiration dates. 2. Written procedures shall be there and include sample size, test methods, storage conditions etc. 3. Stability samples shall be pack in stimulated market container.
Ic
GMP:-
GMP: Good manufacturing practices.
CGMP: Current Good manufacturing practices.
GMP Rules are about care and attention to ensure the things right and keep them right.
GMP Rules:
Be sure you have written correct instructions before any job is started.
Ensure that the correct materials are being used.
Always follow those instructions exactly.
Ensure that correct equipment being used and that is clean.
Prevent contamination and mixed.
Always guard against labeling errors, always use proper labeling
Always work accurately & precisely
Keep things clean & tidy
Find out the mistakes, errors & bad practices & report them immediately.
Make clean & accurate records of work done.
Applicability CGMP regulations:
If the person engages in only some operations subject to the regulation in this part that person need only comply with these regulations applicable to operations in which he or she is engaged.
GLP: Good Laboratory Practice:- Regulations relating to the conduct of toxicology studies, especially in the use of laboratory.