GxP and cGxP in Bio/Pharmaceutical Industry

GxP and cGxP in Bio/Pharmaceutical Industry Prof. Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM – 590010, Karnataka, India E-mail: bknanjwade@yahoo.co.in Cell No: 00919742431000 Department of Pharmaceutics

GxP • The bio/pharmaceutical industry has created its own language and GxP is one of many acronyms that we all tend to use. • While this may seem “elementary” to some of you, many people may not know what this means. • G = Goodx (variable replaced with Manufacturing, Clinical, Laboratory, Storage, Distribution and Review) P = Practice Department of Pharmaceutics

GxP • As you can see, GxP is used as short-hand form for referring to the regulations established by the United States Food and Drug Administration which are published in the Code of Federal Regulations. • Sometimes people refer to the “GCPs” which specifically regards the rules that govern clinical trials vs. product manufacturing (GMPs) or laboratory regulations (GLPs). • Together, these are known collectively as the “predicate rules” that govern a wide spectrum of regulatory obligations across this diverse industry. Department of Pharmaceutics

GxP • GxP is also where citations emanate from (typically) as regards FDA inspections. • When a regulation is cited, the title tells you where it is published. For example: 21 CFR 312.2 Means:21 = Title 21CFR = Code of Federal Regulations312.2 (312 = part and 2 =section) Department of Pharmaceutics

Lifecycle Requirements Department of Pharmaceutics

GxP • “GxP” is a collective term for the Good Practice quality guidelines and regulations used in many fields, encompassing such internationally-recognized standards as GMP, GCP, GLP, GSP, GDP and GRP. • GxP guidelines are designed to ensure that products are safe, meet their intended use and, in regulated industries such as drugs, food, medical devices and cosmetics, adhere to quality processes during manufacturing, control, storage and distribution. Department of Pharmaceutics

GxP • GxP is a general term for Good Practicequality guidelines and regulations. These guidelines are used in many fields, including the pharmaceutical and food industries. • The titles of these good practice guidelines usually begin with "Good" and end in "Practice", with the specific practice descriptor in between. • GxP represents the abbreviations of these titles, where x (a common symbol for a variable) represents the specific descriptor. Department of Pharmaceutics

Core GXP Information Department of Pharmaceutics

Regional Harmonization Initiatives Department of Pharmaceutics

GxP Department of Pharmaceutics

List of GxP’s in Pharmaceuticals • GMP – (Good manufacturing Practice) • GCP – (Good Clinical Practice) • GLP – (Good Laboratory Practice) • GSP – (Good Storage Practice) • GDP – (Good Distribution practice) • GRP – (Good Review Practice) Department of Pharmaceutics

Purpose of GxP • The purpose of the GxP quality guidelines is to ensure a product is safe and meets its intended use. • GxP guides quality manufacture in regulated industries including food, drugs, medical devices and cosmetics. The most central aspects of GxP are: • Traceability: the ability to reconstruct the development history of a drug or medical device. 2. Accountability: the ability to resolve who has contributed what to the development and when. Department of Pharmaceutics

Regulators Department of Pharmaceutics

GMP – (Good Manufacturing Practice) Department of Pharmaceutics

What is GMP ? • GMP is that part of Quality assurance which ensures that the products are consistently manufactured and controlled to the Quality standards appropriate to their intended use • A set of principles and procedures which, when followed by manufacturers for therapeutic goods, helps ensure that the products manufacture will have the required quality. Department of Pharmaceutics

Good Manufacturing Practices • A basic tenet of GMP is that quality cannot be tested into a batch of product but must be built into each batch of product during all stages of the manufacturing process. • It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. • Some of the main risks are unexpected contamination of products, causing damage to health or even death • In correct labels on containers, which could mean that patient receive the wrong medicine. • Insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects. Department of Pharmaceutics

GMP QA GMP QC Department of Pharmaceutics

GMP • GMP is the magic key that opens the door of the Quality • In matter of GMP, swim with the current and in matter of Quality stand like a rock! Department of Pharmaceutics

GMP GMP Is that part of Quality Assurance aimed at ensuring that products are consistently manufactured to a quality appropriate to their intended use Department of Pharmaceutics

GMP guidelines • GMP as per Schedule “M” • GMP as per WHO • GMP as per MCA now known as MHRA • GMP as per TGA • GMP as per US FDA • GMP as per ICH guidelines Department of Pharmaceutics

GMP guidance documents • EU Good Manufacturing Practice (GMP) Guidelines, Volume 4 of “The rules governing medicinal products in the European Union” • US FDA current Good Manufacturing Practice (cGMP) for finished pharmaceuticals, 21 CFR, 210 and 211 • WHO Good Manufacturing Practices for pharmaceutical products, Annex 4 to WHO Technical Report Series, No. 908, 2003 Department of Pharmaceutics

GMP • GMP in solid dosage forms • GMP in semisolid dosage forms • GMP in Liquid orals • GMP in Parenterals Production • GMP in Ayurvedic medicines • GMP in Bio technological products • GMP in Nutraceuticals and cosmeceuticals Department of Pharmaceutics

API Manufacturing Process Department of Pharmaceutics

Secondary Manufacturing Dosage Forms Department of Pharmaceutics

Secondary Manufacturing Process - Tablets Department of Pharmaceutics

Secondary Manufacturing Process – Sterile parenteral for injection Department of Pharmaceutics

Packaging Department of Pharmaceutics

Biotechnology Manufacturing Process Department of Pharmaceutics

Ten Principles of GMP • Design and construct the facilities and equipments properly • Follow written procedures and Instructions • Document work • Validate work • Monitor facilities and equipment • Write step by step operating procedures and work on instructions • Design ,develop and demonstrate job competence • Protect against contamination • Control components and product related processes • Conduct planned and periodic audits Department of Pharmaceutics

Beyond GMP • Reduce pollution - Zero discharge • Adaptation of environment friendly methods • Consideration for better and healthier life tomorrow • Consideration of ethics in life • One should begin with end in mind otherwise it will be the beginning of the end Department of Pharmaceutics

Cost of effective GMP • In fact Cost benefits – positive cost benefits of GMP/QA • Good plant lay out, Smooth work flows, Efficient documentation systems, well controlled process, good stores lay outs and stores records- These are Good manufacturing practices • Reduction in work in process and inventory holding costs • Avoidance of cost of Quality failure ( cost of waste, of rework, of recall, of consumer compensation and of loss of company reputation Department of Pharmaceutics

Cost / Benefit analysis • GMP is not an “On-cost”. • It is not even “Just free” • It is a contribution to profit • Good manufacturing Practice is also Good management Practice leading to Good Manufacturing Profit • GMP is central and basic and has cost benefits ( not to be considered as extrinsic or imposed upon manufacturing activities) Department of Pharmaceutics

Cost / benefit analysis • Cost of quality = Cost of A – Cost of B- Payback from C = Profit A B C Staff Scrap Improved morale Training Rework Motivation Systems Complaints Faster throughput Documentation Chaos Higher productivity Equipment Lost sales Increased sales Maintenance Recalls lower inventory Calibration Closedown Sampling Testing In process control Validation Auditing Department of Pharmaceutics

GCP – (Good Clinical Practice) Department of Pharmaceutics

What It Is GCP • An international ethical & scientific quality standard for designing, conducting, recording & reporting human clinical studies • EU • Japan • US • Applies to registration studies that may have an impact on safety & welfare of human subjects Department of Pharmaceutics

GCP Participating Parties • IRB/Ethics Committee • Investigators • Sponsor • Regulatory Authorities Department of Pharmaceutics

GCP Key Documents • Investigator Brochure • Study Protocol • Informed Consent Document Department of Pharmaceutics

GCP Principles • Studies in accordance with Declaration of Helsinki; consistent with GCP & applicable regulatory requirements • Studies initiated & continued only if anticipated benefits outweigh risks • Rights, safety & welfare of human subjects take priority over interests of science & society • Available non-clinical & clinical info on product adequate to support study Department of Pharmaceutics

GCP Principles • Studies scientifically sound; described in clear, detailed protocol • Study in compliance with IRB/EC approved protocol • Medical care given to subjects is the responsibility of qualified medical professional(s) • Individuals conducting studies qualified by education, training & experience • Freely given informed consent obtained from every subject prior to study participation Department of Pharmaceutics

GCP Principles • Study information recorded, handled & stored to allow accurate reporting, interpretation & verification • Confidentiality of subject records protected in accordance with applicable regulatory requirements • Investigational products manufactured, handled & stored in accordance with GCP & used in accordance with approved protocol • Systems/procedures implemented to assure quality of study Department of Pharmaceutics

IRB/EC Roles & Responsibilities To safeguard study subjects’ rights & welfare by: • Evaluation/disposition of study proposal • Evaluation of proposed subject consent materials • Evaluation of emergency use consent methodology • Evaluation of investigator qualifications • Ongoing review of study progress (at least yearly) • Evaluation of proposed subject compensation plans Department of Pharmaceutics

IRB/EC Composition & Operations • Membership has qualifications & experience to evaluate science, medical aspects & ethics of proposed study • ≥ 5 members • ≥ 1 member whose primary interest in nonscientific • ≥ 1 member independent of institution or study site • Written SOPs & records • Decisions rendered at announced meetings with quorum in attendance Department of Pharmaceutics

IRB/EC Composition & Operations • Only members participating in review should vote • Investigator may provide info on study, but should not be involved in review or vote • Nonmembers with expertise in special areas may be invited to assist with review (but cannot vote) Department of Pharmaceutics

IRB/EC Procedures • Document group membership & qualifications • Schedule meetings & notify members • Conduct initial & ongoing review of studies • Determine ongoing review frequency • Provide expedited review of minor study changes, in accordance with regulatory requirements • Specify that no subject should be enrolled in study prior to IRB/EC approval Department of Pharmaceutics

IRB/EC Procedures • Specify that no deviations from protocol should be initiated without prior IRB/EC approval • Emergency situations require immediate notification of IRB/EC after the fact • Specify that Investigator should promptly report: • Protocol deviations • Changes increasing subject risk or study procedures • Serious and unexpected adverse events Department of Pharmaceutics

IRB/EC Procedures • Notify Investigator promptly of: • Study-related decisions • Reason for decisions • Procedures for appeal of decisions Department of Pharmaceutics

IRB/EC Required Records • Relevant records maintained ≥ 3 yr after study completion • Records available for review by regulatory authorities Department of Pharmaceutics

IRB/EC What is Reviewed • Investigator Brochure or Report of Prior Investigations • Study protocol & amendments • Investigator qualifications • Informed consent documents, including subject recruiting tools • Other written information provided to subjects • Subject compensation plans • Adverse events • Protocol deviations Department of Pharmaceutics

GxP and cGxP in Bio/Pharmaceutical Industry

GxP and cGxP in Bio/Pharmaceutical Industry

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