The biopharmaceutical industry is developing quickly and the quality systems are getting increasingly stringent so that margin of errors during selection, screening, processing, packing, testing, release and logistic support are becoming the crucial drivers.
From concept to realization the whole process in this industry depends on crucial selection of vendors and timely execution of the project plan thus making it regulatory compliant. The Project Managers, Production Teams and Quality Control & Assurance groups formulate a plan and this plan will be crucial in bringing the product to market.
Vendors have different working philosophies based on the geographical location and product types they work with. It is better to understand the quality philosophy and compatibility during successful Vendor and Qualification processes.
The biopharmaceutical industry in general needs the following types of materials for building and processing of materials:
- Civil contractors
- Architects
- Compliance consultants
- HVAC & Utility systems, Security systems, Alarms Etc
- Electrical systems
- Bioreactor (Traditional SS Bioreactor, SUB Etc.)
- Chromatography systems (MPLC, Process HPLC Etc.)
- IT systems (Process support, Electronic BMRS, Data Storage Etc.)
- Cell disruption and Harvesting (French press, TFF Etc.)
- Mixing tanks and transportation systems
- Cooling systems and Cold rooms
- Sterile Fill finish equipment and Suits (Includes Freeze driers)
- Quality Testing Equipment (IR, UV, HPLC, FTIR, NMR Etc.)
- Validation equipment and Validation support
- Training support
- Excipients, API’s, Disposables, Testing Chemicals and Mol-bio Reagents
- Primary & Secondary packing materials
This list is not limited, you can add many items depending on the complexity of the molecule one manufactures.
The Vendor selection and Qualification process revolves around three important issues:
- Criticality
- Capacity
- Competition
Criticality
This is the Primary concern for a highly regulated Bio-Pharmaceutical Industry. There are many key drivers in this. This is where you find suitability factor in a vendor and make a final decision which qualifies them.
1. Source of Materials in case of critical API’s & Excipients:
Companies are very keen in knowing the source of starting materials and API’s if it is a Chemical, Biological or an Animal source. The reason is animal sources are being discouraged largely by WHO because of Bioburden constraints, Endotoxin limits, Viral contaminations and Prion issues. Generally all materials will be keenly analysed for monitoring, key steps that are controlled during manufacturing of these materials and contaminations associated from Equipment and Environment. If it is biological in origin it must be proved that contamination from host cells are properly removed by a validated technique. (Host cell protein contamination & other related impurities).
2. Process issues are normal to every company today:
The materials used directly in process should not induce any degenerative effect on the biological cells and should not decrease expression of intended materials both on the cells and interfere further in purification process in the downstream trains.
3. Manufactured:
These materials in use must be properly manufactured, tested and released based on ICH guidelines and shelf life study and stability data must be in place.
4. CQP’s:
Companies clearly look into Module 3 in a CTD document where quality information is given. EU, Japan and US all have these in a regulated flow of information and each critical material will be looked by a multi plant or site vendee in these places as a separate case depending up on critical quality parameters in the final biotechnology derived pharmaceutical.
5. Electronic Batch Records:
Issues like compliance with regulatory guidance (EU Annex-11, 21 CFR part 11, GAMP 5), ease of training, quick qualification and placing the electronic Batch Manufacturing records (eBR’s) in shop floor. The biopharmaceutical industry is now looking more and more at introducing eBR’s to streamline the manufacturing process.
6. Rouge:
Most of the biopharmaceutical industry knows about rouge that is caused by water or steam systems when they come into contact with stainless steel materials. There is no specific guidance from FDA on this subject, yet a big discussion is taking place in the industry about this matter and the use of specific grades of stainless steel and polishes required to overcome this issues. Some big industries are taking this as a critical issue and have started to qualify the critical process equipment that can detect migratory rouge in Biopharmaceutical water systems. This is a critical factor for all biopharmaceutical ancillary equipment suppliers and water system suppliers.
7. Quality Policy:
Companies can insist that vendors disclose their quality policies, internal audits, regulatory comments and also audit results from other potential customers they have. They can question the vendor if a particular set of parameter in a process is modified on a request of a particular customer. It all depends up on confidentiality process and agreements.
8. cGMP’s:
Most of the Process materials used in purification process do not have any specific legal requirement. They comply with internal GMP’s and DN ISO standards. Excipients and API falls under GMP requirements, USP, EU pharmacopeia requirements and especially EU Directive 2004/27/EC for Excipients & ICH Q7A for API’s.
Capacity
This is the second major issue that has impact on the selection of materials. Most of the clients look for a long term and stable relationships with vendors. These issues relate to:
1. Quality Agreements:
Companies may need certain excipients or certain API’s in bulk quantities on a regular basis. This decision will be based on the marketing muscle of the manufacturing company and its selling domain. Often vendors need to increase the capacities of production and the vendee will sign special quality agreements with vendors based on dispatch frequencies, packing material size and specification, stability issues, transport conditions and logistic supports, quality parameters, sampling and rejection methodologies.
2. Disposables:
This is often seen with disposable manufacturers too. For example when a vendor is qualified to sell certain disposable materials that are critical in Biopharmaceutical manufacturing, the vendee looks into various quality parameters, validation, quality certifications, frequency and capacity to supply suitable quality materials regularly becomes a key issue. In the event of increasing the capacity of a particular process the vendee needs to have a suitable quality arrangement document in place to receive increased number of disposables from vendors and expect that there is no deviation in quality, traceability, regulatory compliance, sterility, integrity with such products. These are critical during selection of sterilizing grade disposable filters, single use bioreactors, single use connectors, single-use stirred tanks, 2-D bags, sterile rubber bungs, sterile vials and dress materials for critical zones.
3. Flexible Solutions:
Capacity issues also play a crucial role when flexible solutions are offered by a vendor. For example if you could automate the whole process of manufacturing, risk assessments, validations and requirement management this would lead to a more stringent process with less errors. The vendee will be content with reducing costs for multiple solutions. In this case the user license agreements must be properly written so that the software can be used in a seamless manner in all locations. Similar concepts can also be sued when a piece of chromatography equipment can work from a pilot level to process level. This allows users to get trained well on all pilot scale production processes and can move to production scales without much trouble. This concept has been properly utilized by biopharmaceutical organizations in selection of single use bioreactors (SUBs) at concept level, which leads to decreasing the space requirements, containments and CIP/SIP costs.
Competition:
This is perceived as a necessary evil to sell quality products in a regulated environment. Competition can be both from the vendee and vendor and depends largely on the situation.
1. Quality Parameters:
At times vendee companies need to launch a particular product or increase the production of a product more than its competitors. This makes them take a quick decision without compromising on the quality parameters.
2. Pricing:
The same situation applies when a vendors sells products in highly competitive markets. At this point the pricing will be very flexible based on the capacity and frequency of order.
3. Quality:
A particular vendor will get maximum price and or maximum acceptability from multiple vendees based on the quality of his product quality parameters and quality management systems they follow internally.
Conclusion
To summarise the industry can and will purchase products that have quality, traceability, good documented evidences, manufactured under proper GMP conditions, in compliance with regulatory agencies, good quality agreements, good product stability and shelf life.
