Organization of QA cGMP compliance BIT 230 Chapters 1 and 2 (Huxsoll) TQM Total Quality Management Approach a company uses day to day 7 strategies Leadership Information and analysis Strategic planning Human resource development and management TQM Strategies continued Process quality management Quality and operational results Customer focus and satisfaction • Often focus is on the customer – so last but not least- customer driven success Quality Assurance A unit that is part of the whole US CFR – United States Code of Federal Regulations- defines the quality unit’s job Approve or reject all materials associated production of any product – includes containers, components, labels, other packaging materials Quality Ensure purity- # 1 goal Also strength and quality New biotech lose site of quality – develop science first, then quality Should be done in parallel to have less problems later Role of QA better established in large pharma Quality Control (QC) within QA QC is a testing function Defined as fitness for use Need to be integrated throughout process Fitness for use divided into several components - next slide; these 4 major components subdivided into further categories - THESE important regardless of product Manage from the top down Upper management sets tone for company style and compliance Biopharm products complex- therefore need “quality of manufacture” CFR definition of QA unit - 7 points (pertaining to a nonclinical lab) 1. Maintain master schedule sheet 2. Maintain protocol records 3. Inspect each phase of study 4. Submit periodic written status reports 5. Ensure SOPs are followed 6. Review final study report 7. Prepare a signed statement (with inspection dates, etc. for final study). QA vs. QC Will discuss more later, but major point of confusion QC function limited - testing methods “Controls the product” in production CFR does not clearly define QC- more of a QA definition Product production QA defines systems and methods to ensure quality of a product- QC tests various aspects of a product as it is being developed Which function: QA or QC? SOP for measuring pH of a production run measuring pH of a production run 3 X daily filling in batch records developing batch record signing and dating batch record confirming integrity of raw material defining raw material to be used in production Routine functions of QA Testing Documentation Labeling Vendor audits Routine QA functions cont’d Raw material receipt Product release Product Specifications Training Other QA Functions 1. Company awareness long and short term goals QA part of business involvement team if QA operates as a separate group company not as successful upper management must commit to QA sometimes overlooked in biotech Other QA Functions cont’d 2. Product knowledge without it failure is likely know the product, process used to develop it, support systems, and product use (e.g. target population- FOSAMAX example - older population, people with arthritis, people with difficulty sitting up) AGAIN, product defined by systems established to assure its consistency Other QA Functions cont’d 3. Facility knowledge function of equipment function of local environment of production facility need personnel expertise in these areas proper training, etc. don’t work in a vacuum Other QA Functions cont’d 4. Networking through outside organizations regulatory agencies other companies with similar product line conferences understand industry and regulatory standards Other QA Functions cont’d 5. Risk analysis/decision making analyze situations make recommendations- if so, assure proper modification of SOP risk/benefit ratio to modification of SOP Page 8 - quality systems functions and percentage at various companies http://www.mtmlaboratories.com/janusmtmportal/portal/temp Establishing QA Define the function of QA (chicken and egg problem) Should start before production of material to be used in Phase 1 clinical trials Start when biotech company is small What quality systems are needed Risks of leaving out some QA functions? New company QA What type of product Complexity of end material Production method Financial considerations Stage of development is product in-licensed? is there some parameters for product development already determined? Factors to achieve Quality Page 9-10 (points 1-12) Key points: Quality indicators discussed not hiddenproblem in other sectors of company, not just quality (e.g. Vioxx, was everything transparent?) resource allocation good exchange of dialogue accept responsibility (e.g., Tylenol case) QA functions Assay development and validation equipment validation process validation vendor qualifications raw material and product specs documentation QC testing People, people, people In-house expertise (product & quality) need for external expertise (advisory, etc.) add staff as need arises proper training other company personnel should be part of day-to-day QA decisions and processes avoid attitude that QA is not needed QA organization Figure 1.3, Page 11 Compares organization at various stages of a company Large pharma has a separate QA department with significant staff Day-to-day goals Setting standards sets standards for goals for both QA group and entire company written especially important for process deviations based on expectations and outcomes for product How is the experience gained with a product? Day-to-day cont’d Implement training can’t really do it here in class- need to be on the job; but learn the basics here (e.g., microbiological procedures - sterile technique) ongoing training needed make time for training (can easily be cast aside) make training a goal (objective) of the employee’s yearly plan- reward built in Day-to-day cont’d Feedback constructive realistic communication key support time commitments and constraints What is your time back up plan? Coming into cGMP compliance Chapter 2 How does a company look pre-GMP? Small company- few to a few dozen employees mostly research scientists very few others as administrative, production, testing and support operating style develops quickly “corporate culture” problems with this during mergers Pre GMP company Creative and fast long hours for employees good interaction react quickly to issues - not much red tape less documentation - many things decided verbally with no paper trail- can lead to problems as the company grows costly GMP compliant company Large pharmaceutical companies many employees in production, testing, support and administrative equal or outnumber R & D scientists follow accepted, validated, approved methods slower to change large volume of documentation Moving from Pre- to GMP Company has identified product to produce; plan needed to develop product under GMP Be part of company master plan site able to produce GMP product or must find alternate manufacturing facility Regulatory affairs personnel - always jobs in this area! Moving to GMP Finalize plan Determine budget (may be when a company goes public) START the project I’ll say it again: documentation! How is the documentation used? GMP required documents Process variables analytical methods used to determine quality of intermediate and final products functioning of support systems facility is functional and suitable clean and functional equipment reproducibility Remember Flu Vaccine problem this past Fall?? Clinical production Need GMP here, too included to document: raw materials labeling batch records equipment/building preventative maintenance Yields Figure 2.1, page 19 GMP training On-the-job training necessary “validation” of personnel trainer content expert; experience as instructor upper management acknowledges the need for on-going training often external trainers brought in (certified) GMP training Audits - internal and follow same GMP guidelines as external audit written and well organized follow approved procedures auditors trained and from outside immediate work area External audits include review of internal audits, although not FDA’s current policy Documents for auditing Master schedule generated up to 2 years in advance may be included in SOP internal audits not surprise but, not a time to do everything at last minute; must perform duties regularly hold post-audit meeting have corrective action and back-up plans There’s never time to do it right, but always time to do it over!