Quality Assurance Systems in Pharmaceuticals manufacturing

Quality assurance for pharmaceuticals is very important aspect in manufacturing of pharmaceuticals. There is following simple points for quality assurance aspects in pharmaceutical manufacturing 1. In process quality assurance 2. Finished product quality assurance. 3. Assuring Quality of ingredients used to make pharmaceuticals Quality assurance is a systematic approach and process where a pharmaceutical which is manufactured is being certified as safe and complying with all standards and regulations and requirements of FDA. It is not just because FDA requires the pharmaceutical manufactured is of good quality, but it is moral responsibility of each personnel associated with pharmaceutical manufacturing in the manufacturing company. The system of quality assurance should be designed to to produce a very good quality pharmaceuticals, the systems developed should be able to prevent all sorts of noncompliance, they should merely not point after a noncompliance has occurred but they should effectively systematized to function as a chain reactions , where in if some failure occurs at any given point the chain should break and alert the concerned person responsible individual. 1.Raw material dispensing 1.During dispensing activity of active pharmaceutical raw material , one should checke 1. Assay of active ingredient 2.Assay calculation , and reports of Material 3.Physical appearance of material 4.Calibration of balances 5.Temperature records 6.Laminar air flow bench cleaning , filter cleaning and pressure and air flow. 7.Condition of Material 8.Tare and net weight while dispensing of material 9.Manufacturing and expiry date of material 10.Cleaning of utensils and scopes used 11.Personal hygiene 12.Status labels over material containers 13.Storage of material. 14.Documentation of all dispensing activity 15. Quarantining dispensed material for days storage aria in proper lock and key arrangement. And so on If listed in proper format, and handed over to the Quality assurance personnel who do dispensing activity , and train them to check these points while dispensing of material , One will be able to point out and rectify almost every critical noncompliances which would prove fatal . Good quality pharmaceutical manufacturing starts with building of quality assurance systems , and raw material quality is the most important aspect of quality of pharmaceutical manufactured by you , above system takes care of all raw material quality issues before is added in to the actual batch of pharmaceutical , you check again assay , and its calculations , and all relevant things about material . While start up of new batch, stringent verification of all cleaning activity, presence of previous products, and labels, packaging material or traces, by doing rinse analysis, and documentation, assures prevention of cross contamination Most of times many noncompliance's are identified and compiled at the point of Dispensing of raw material itself .

2. Addition of active ingredient Addition of active ingredient in presence of quality assurance personnel. This activity too is very important in manufacturing of pharmaceuticals. Quality assurance personnel checks dispensing activity of raw material, assay report and calculations, etc. QA person checks addition of raw material in his presence, and certifies that the material is properly added in the batch along with production personnel and documents. 3.Water is the very important ingredient in pharmaceuticals , hence its microbial quality and report should be verified every day by QA , we suggest to carry out test for acidity and acidity and alkalinity as this test is very peculiar , even the PH and conductivity are complying sometimes you may find that test for acidity and alkalinity giving results which are not complying , this is rare in todays highly efficient water systems available but , incorporate this in your day today quality assurance monitoring . 4. Volume make up and weight of bulk This aspect too is very important. Verification of volume make ups and final weight of a batch by quality assurance personnel is very important activity these activities takes care of all sorts of errors due to volume & weight make up. 5. In process fill weight and fill volume checks. So far we discussed about 1 , Dispensing of raw material , Addition of active material in to batch 3.Volume make ups and weight variation of bulk products At all steps QA is on the lead front . Final process of filling in case of liquid dosage form and weight, and weight variation checking in case of compression of tablets, ensures that the dosage form is properly compressed, formed, and filled; the active material too was checked and found of good quality before addition to batch. The water used too is verified. 6.Releasing of Batch System to release a batch of pharmaceutical to market should include verification of Finished product analysis report. Microbial load test results , and assays of active ingredients , Batch manufacturing record Sterility test reports in case of injectables Review of records of all steps from bulk manufacturing to packing . Yield analysis Pack line check list for verification packing activity. 7.Online packing line check list: This is a very important system , in most of the pharmaceutical companies we have seen this system. This consist of online packing activity checking format , which requires that a quality assurance person to check all the points of packaging activity and document them in a proper way while the packing activity is going on , just as described for manufacturing stage , a good format developed to cover all activities in packing line , provides a assurance of quality for pharmaceuticals manufactured in your company. we have a sample document format loaded over this website find it here. 8.Stability testing :

9.Annual Product Quality Review : 10.Challenge QA system to validate its complete effectiveness :We recommend you to adapt a challenge validations at each and every point in your quality assurance systems, What is meant by challenging a effectiveness of validity of a working system:One should challenge a quality assurance systems we described in brief , to make sure that these are working properly , the system , the trained peoples , the environment responds in positive manner to a challenge placed in to the system to identify any type of discrepancy while manufacturing or process , The defect , or discrepancy is identified and rectified in proper way for which a quality assurance system is made for. For example We have seen peoples who can identify a defective ampule of a injection in the process of visual inspection once it is knowingly placed with a peculiar marking in to the complete batch , a trained person is able to remove the defective ampule very effectively , likewise a QA in process QA personnel is also able to find any discrepancy , if the format of inspection is properly made and asked to fill by doing proper exercise . We have provided all sorts of formats and guidance for above 7th and 8th points and other Quality assurance aspects in pharmaceuticals over this website. The Quality Assurance Department should design and operate quality assurance system in such a way that they derive the quality of manufactured product by the designing of there quality assurance systems, the system in place generate best quality pharmaceuticals Similarly Quality Assurance System designed for , cleaning, personnel hygiene, personnel training, line clearance, validations are equally important which are discussed in depth with sample documents over this blog in earlier posts.

Quality by design in pharmaceuticals, understaning concept of quality by design

What is concept of quality by design This concept is misunderstood by many peoples , we are tyring to put this in a very simple words and we are giving a document published by FDA on quality by design concept ,for your reference you will find a link at the bottom of this article you can take printout of this and keep in your library. In pharmaceuticals so far we put stress on after and in process inspections , put step of inspection at all points, assuring the process carried out is meeting the standards, product manufactured is meeting the standards, But in the quality by design concept it is said that , instead giving stress on inspection rather you can plan the quality of your pharmaceutical dosage form that you are going to manufacture. It is a great concept , planning the quality of pharmaceuticals. We know everything about 1.Materials: You need to look in to the chemistry of the material , which is the important aspect of your raw material , (Related substance affecting the formulation) so knowing these we can plan the raw material quality. This also involves designing your packaging material which will provide best quality product. 2.Machinery : we know what is the best machinery for getting good quality product There should not be any manual handling of material by man , everything should be automatic process. 3.Process : We know which is the best process for our pharmaceutical dosage form. Think up on how you can develop it to best one , plan the process well , design the process well , which will design quality .

4. Controls : You know which are the critical controls to be cheeked while the process is going on as well as before starting the manufacturing . These process controls should be designed to yield best quality pharmaceuticals . automation of quality control process . 5.Where and how this concepts can be applied:Area of implementation of quality by design concept is very broad and can be applied to each and every unit operations in pharmaceutical manufacturing .right from the chemistry, manufacturing, and controls. Example while in compression of tablets, if there is higher or lower weight, your machine should alert you , and stop compression unless it is intervened and corrected. Here there is no scope for manual interference in passing deviation, machine has to be designed to yield the quality of product, which requires planning of what quality you want , This concept brings in lots of other science fields to help design the quality of pharmaceuticals. FDA had invited pharmaceutical companies to participate in their pilot program which they say is to gain more information on and facilitate agency review of quality-by-design, risk-based approaches for manufacturing and developing guidelines for and principles of quality by design and risk management in pharmaceutical manufacturing.

Regulatory Affairs in pharmaceuticals manufacturing

Regulatory Affairs in pharmaceuticals (RA in pharma), also known as Government Affairs( Pharmaceutical regulatory affairs in pharmaceutical industry), this field in pharmaceutical industry is dealing with all aspects of government affairs , submitting products, getting license and registration of pharmaceutical products for sale and everything. Regulatory affairs departments are there in most of the regulated industries, like pharmaceuticals industry, medical devices, energy, and banking. What is Regulatory Affairs In Pharmaceutical Industry:Regulatory Affairs (RA) is one of profession in pharmaceutical industry with great potential and opportunities , most of the pharma , biomedical ,companies in world have Regulatory Affairs department in their company. Regulatory Affairs profession in short can be described as process in a pharma company to collect, Analyze and Communicate the Benefits and the Risks and of a given Pharmaceutical or health care product to public as well as regulatory agencies all over the world. Responsibilities of Regulatory Affairs (RA) involves collecting data , analyzing and preparing and presenting documents for registration to regulatory authorities and perform all subsequent dialogue to gain and maintain marketing authorization (MA) for the products Pharmaceutical or health care product. Hence the Regulatory Affairs professionals are required to continue a track of every chang happening in the laws and legislations in the countries where a product is being marketed or a company is going to market its product. Regulatory Affairs (RA) professionals not only do registration of pharmaceutical products, but they give an opinion to Pharmaceutical companies technically as well as strategically . They are involved right from right from development of a pharmaceutical product to manufacturing, marketing as well as post marketing studies . Advice of a regulatory Affairs on legal and technical requirements saves lot of money and time for a pharmaceutical company right from developing to the production and marketing the same. Regulatory Affairs as Career:World over pharmaceutical industry is one of greatly regulated industry and there is great demand for peoples manages regulatory affairs.

Pharmaceutical Regulatory Affairs professionals have responsibility in following areas: 1. To Ensure that their companies comply with all of the regulations and laws pertaining to their business. 2. To Work with federal ,central , state, and local regulatory bodies and personnel on specific issues associated with their business, working with such agencies as the Food and Drug Administration ,European Medicines Agency (pharmaceuticals and medical devices) 3. To advise their company on the regulatory affairs and climate that would affect proposed activities. describing the "regulatory climate" around issues like the promotion of prescription drugs compliance. Pharmaceuticals industries were the first to be significantly regulated in the modern era. In 1980 the European Community (European Union) started the regulation of health care products in the member countries. The concept of regulating medicines was well established in most member countries along similar lines to the US. Pharmaceuticals and Health care or Pharmaceutical Regulatory Affairs Profession is still an emerging profession but has two major international professional membership societies: The regulatory professional typically has a background relevant to the business in which they work, i.e., science, medicine. Pharmaceutical regulatory affairs is a field in pharmaceutical industry which has good scope as the personnel is trained all topics related to pharmaceutical manufacturing and its regulation in various countries. The concern person is responsible for providing all technical data to pharmaceutical regulatory agency where he want to register the pharmaceutical product for sale, hence he must have knowledge 1. About Pharmaceutical Administration and Management, 2. How to Handling laboratory and manufacturing deviations 3. Pre approval inspections, 4. About Impact of Total Quality performance 5. GMP Certification and enforcement actions, 6.Maintenance and Update of Product Master Files , 7.Internal Compliance of Documentation 8.Coordination and Assembling of CTD/eCTD, 9.Quality systems, 10.Quality Assurance, 11.Method Validations, 12.Process Validations, 13Master Validation Plan, 14.Protocols 15.Standard Operating Procedures (SOPs) 16.Auditing and Compliance Functions 17.Regulatory strategies 18.Regulatory agencies 19.legislation and documentation systems as required for USFDA, UKMCA/UKMHRA, MCC, WHO etc. , FDA/UKMHRA Queries and submission , 20.Application requirements and guidelines , 21.Electronic submissions , 22.Medical device regulations , 23.Stability as per ICH ,guidelines & MBRs; International harmonization , Practice of regulatory affairs, 24.USP, Pharmacological, Toxicological and Clinical Trial Information, Re-registration Documents Design, 25.Role of the International Business Operations of the Pharmaceutical MNCs in Attracting the FDI, 26.Clinical Pharmacy, 27.Drug Trials and Vaccine Trials Guidelines,

28.Drug Laws , 30.IND training , 31.How to Format, assemble and submit the NDA, Human Genetic Research, 32.Clinical Trials, 33.Indian Ethics Committee, 34.Good Clinical Practices (GCP), 35.Pharmaco-vigilance and ADR reporting , 36.Clinical Trial Regulation, 37.Intellectual Property Rights, 38.Basis of Patentability, 39.Patent Application Procedure, 40.Compulsory License, 41.Infringement of Patents, 42.Product Registration for Regulated and Non Regulated Markets etc. There are many agencies which offer course in Pharmaceutical regulatory affairs. If you are a pharmacy graduate , and it is always advantages to enroll for a course which in teach you basic things about regulatory affairs in pharmaceutical industry for dealing with requirements of all countries. There is good scope for Pharmaceutical regulatory affairs personnel for pharmaceutical industry , which is looking for registration of its products and selling its products in USA , Europe , and African countries , these activities require dedicated peoples and this activity is very important for pharmaceutical company , hence they pay good salaries to pharmaceutical regulatory affairs peoples. we are providing some good documents to my fellow pharmacists working in regulatory affairs in pharmaceuticals manufacturing. These will be very useful references for pharmaceutical regulatory affairs. Validation of Cleaning process Master document sample pharmaceuticals water system validation sample document Water system validation sample document Purified water system DQ IQ PQ and actual validation document sample (Copy and paste in excel , in pasting option select match destination formatting) Change control In pharmaceuticals master document as a sample 1st format Installation qualifications of any machinery used in processing of pharmaceuticals manufacturing Change control format. second format SOP for Microbiology (There are two sheets there copy and paste in excel , in pasting option select match destination formatting) Sample Document of Installation Qualification of a pharmaceutical machinery Pharmaceutical Product validation master plan. Check list for inspection and Quality audit of your pharmaceutical manufacturing unit CGMP guidelines will get detailed here

Quality by design concept and Pharmaceuticals Formulations

Quality by design concept is well understood for pharmaceutical manufacturing machinery's and process . Quality by design concept not only demands machinery and process disigning for quality but also puts stress on designing chemistry of your product so as to build a far better quality product. Quality by design concept requires that the quality of a pharmaceutical product should be inbuilt , and the designing of process , machinery , and formulation should yield the final product of best quality ,and its quality is not dependant on later inspection and controls , but it is getting produced as per you plan . 1.Planing the quality 2.Design the quality

Example 1 Design a machinery with auto sampler , which will provide you a samples of your final product automatically , from all level for all time intervals , which represents complete batch and process of a pharmaceutical dosage form , this provides better accuracy of control , than human inspections. Quality by design concept requires that not only machinery but other aspects of your formulations are needed to be designed to get quality of final product. This is a best idea Quality by design for pharmaceuticals manufactured. You have the ability to design your formulation which should yield best quality final product. You have to plan your quality of final product while you are designing your formulation. Instead of putting stress on in process quality checkings and inspections This is what chemistry part of guidelines says. Example 2 I will like to give an example how you can design a formulation to yield best quality. Consider your final product is stable at PH 5.5, and a little fluctuation in final PH of your product gives you lot of problems . While adjusting the final PH , your formula has given buffering agents quantities just sufficient to adjust the PH , and manufacturing person has access to more than required quantity of buffering agent. You have opportunity to design the quality here, by limiting the quantities of buffering agents. Fix the quantity of the Buffering agent in the range of limit of +0.3 for final product Now you have limited the access of manufacturing pharmacist to usage of buffering agent, he will use just sufficient quantity, and not quantity sufficient to adjust the PH of your final product. This requires pilot as well as actual validations, and one it is set, your product will not have fluctuations in PH in wider range this will be always in the very small range of +0.3 This is true for other aspects of formulations too. Putting limit on impurities in Raw material Say a raw material is very critical for your pharmaceutical product. You get this material which compiles the pharmacopoeial limit for impurities. But give lot of problems while in actual process. You can design your limit of passing of this material test for impurities in the more strict range than that of pharmacopoeia. You can develop your own method to analyze these impurities in the raw martial itself in better way so that you can ask your raw material manufacturer to make the material with your limit. There are lots of tests which you can design to get best quality pharmaceutical product.