Scale-up experimental batches...GMP Batch approaching the GMP drug product manufacturers.............. updated on May 7, 2005.
PREPARATION FOR SCALE UP GMP BIOBATCHES AT MANUFACTURING LABS Zhion, May 2005
The first step is to find out which contract manufacturers are able to manufacture your clinical or registration batch. Here is an outline of the information that you should prepare to them for the first contact and obtain a rough idea of the manufacturing cost:
1. Name of the active ingredient You should also provide the MSDS (toxicity information) to them. You should mention who will test and release the active ingredient.
2. A list of all inactive ingredients, And, let them know if you will provide the materials and who will test and release the materials.
3. A list of equipment needed for the process. You should spell out exactly what type of equipment, e.g. vertical high shear mixer or horizontal mixer. The granules made can be very different.
4. Process Outline. You should also include batch size for each step. For compression, you should mention if you have the toolings.
5. In-process Samples and Experimental Test. If you require them to perform in-process test before moving to next step (e.g. blend uniformity before compression, you need to let them know in advance.
6. Stability Test Stability test is a "must" for all clinical trial materials including pilot batch. You need to let them know if they need to perform such testings.
After you get quotes from various manufacturers, you should initiate a GMP auditing on these manufacturers including reviewing their FDA citations. There are fourteen basic questions you should address to them before your inspection on their facilities:
14 BASIC QUESTIONS FOR THE GMP CONTRACT MANUFACTURERS:
1. Does the facility operate in a state of control as defined by the GMP regulations? 2. Does this facility operate under a facility quality policy? 3. Is its Quality Assurance unit a separate organizational entity Â§211.22(a)? 4. Can this Quality Assurance unit approve or reject the products Â§211.22(a)? 5. Does the QA unit routinely review batch records Â§211.22? 6. Are adequate laboratory space, equipment, and personnel to run testingsÂ§211.22(b)? 7. If a contractor is involved, has it been inspected? 8. Date of last inspection:____________________ 9. Are all QA procedures and responsibilities in writingÂ§211.22(c)? 10. Are all procedures current and approved? 11. Are the procedures recorded? 12. Are QA supervisory personnel qualified by way of training and experience Â§211.25? 13. Are other QA personnel, qualified by way of training and experience Â§211.25? 14. Has this facilities been inspected by FDA? 15. Did they receive any warning letter (483) from FDA?
If the answers for all these questions are positive, then, you may initiate the GMP facilities auditing. If you do not have the experience, you should hire qualified GMP consultant to process the job.
THIS ARTICLE IS FOR YOUR REFERENCE ONLY. YOU SHOULD CONSULT YOUR GMP CONSULTANTS BEFORE SCALE-UP MANUFACTURING ANY GMP BIOBATCH.