Audit Observations:Root causes of failure External factors Cultural Behavioral Internal factors Structural Attitudinal Competency Knowledge based

External factors No discipline No respect for the law No idols or models for good behavior in the society Significant lack of - Hygiene Safety Civil behavior The way we behave outside

So …. The gap What we do outside What needs to be done INSIDE IS FAR TOO DIFFERENT !

Internal factors Owner – - Hands on - Commercial interests - Very little respect for Quality - DOESN’T WANT TO “INVEST” IN GMP CEO – - Looks after marketing & finances - With an eye only on production and new products - Very little respect for Quality Structural

- Or at least the plant head is a Quality assurance person? Quality is only audit-centric and not product-centric Do you know a company where – - Head of the company [CEO] is a Quality assurance person?

ORGANIZATIONAL CHART VALIDATION/ CALIBRATION PROCESS EQUIPMENT CLEANING FACILITY COMPUTER CALIBRATION CAPA OPERATION IPQA BLENDING FILLING QC EMP/MICRO ENGINEERING WAREHOUSE LABELING/ PACKING/ DISTRIBUTION COLD ROOM FREEZERS VENDOR AUDITS SITE QA HEAD FG BATCH RELEASE SYSTEM CHANGE CONTROL DEVIATION OOS / OOT COMPLAINTS RECALLS TRAINING MEDICAL APR/APQR INT. AUDIT EXT. AUDIT CAPA DOCUMENTATION BPRS/ANNEXURES MFRS/MBR SOPS LOG BOOKS VALIDATION SYSTEMSLABELS QUALITY AGREEMENT IQ,OQ, PQ (DOCUMENTS) URS SMF JOB DESCRIPTION

Internal factors continued … Attitudinal – In denial mode – when hit by audit, DON’T WANT TO LOOK WITHIN. Tendency to short-cuts, jugaadbaji Not completing documentation on line and on same day Preference only to the production, batch-making. Everything else is kept pending or postponed - till last 7 days before an important audit. PM and calibration never done on time. GMP CAN WAIT !

Internal Factors continued … Competency – Unavailability of competent manpower Inadequate salaries for deserving candidates Pennywise pound foolish (long term benefits of GMP & quality) Use of outside experts, consultants is done only after audit failure or just close to important audit rather than preventive or strengthening basis.

Internal factors continued … Knowledge – The lack of knowledge - subject knowledge - Logic behind various processes - Technology NO ONE WANTS TO QUESTION THE WHYS AND HOWS OF PROCESSS, GO IN DETAILS WHICH HAMPERES INVESTIGATION IF BATCH FAILS. e.g. In sterile operations, knowledge of basic microbiology is essential. e.g. Knowledge of basic tablet technology is important to understand the ‘why?’ behind the processes.

When knowledge is lacking….. You start …. Avoiding Evading Hiding Short cutting IF WE KNOW THE WHY’S AND HOW’S OF THE PROCESS AND FAILURE… IT IS EASY TO FACE THEM AND SOLVE THEM RATHER THAN AVOID OR HIDE THEM. !! This is where the QA comes in.

Most problems in audit are because – They are hidden from QA. Production has no confidence on QA. QA is seen as outsiders and no less evil than the auditors.

QA - Friend, Not a Foe !! QA acts as a barrier and production also looks upon them as Barrier …… And not a solution provider. Most QA people themselves do not know this fact. QA can give systemic solutions to all problems in the plant.. Except problems with recruitment, increment, promotion and removal of a person. QA is an enabler of production. Not a barrier.

But… Problems with QA They do not read manufacturing SOPs or PDR of a product. They do not go into details of science of drug manufacturing and microbiology They are not empowered sufficiently by the management They do not take up responsibility of partnering with manufacturing. They do not take regular rounds on shop-floor.

Tools of QA Change control Incident reporting Planned/ unplanned deviations OOS, OOT, OOL Self inspection CAPA, APQR

Role of QA Encourage production to report incidences, deviations Encourage the culture of openness Be bold and cooperative where needed. Win trust/ confidence of the production Read and understand all production SOPs Help in root cause analysis and CAPA implementation Provide valuable inputs and solutions [Not be just a document signing machine – Be it SOPs, logbooks, CTDs etc] Help in making guide lines Harmonization of policies on which operating persons can build their documents.

SOP s SOPs not at work stations but in drawers SOPs cut & pasted from previous plants SOPs are not read by the ‘doers’ Poor understanding of the science and logic – SOPs are not mere laws and rules to fear them. Common Root causes of failure

Common root causes of failure continued …. CSV expertise not available within the plant Delayed and then backdated documentation Poor understanding of the factors affecting the product quality and patient safety QA is not taken in confidence when such need arises.

Common root causes of failure continued …. Ignoring simple GMP/QA principles while filling batches, manufacturing tablets, capsules Top management always thinks that GMP and ETP are unnecessary and waste of money. Neglect of GMP does not rebound / boomerang everyday but when it does, it is fatal, (while tablets, capsules, ampoules, vials are quantifiable every day !)

Common root causes of failure continued …. MQR meeting are not held at all or not taken seriously by the plant head upwards. Self inspection/IPQA is weak, very junior persons in QA are asked to “Go and check Production”. No check list. OR – If strong, then points just keep piling up without CAPA or end action. So QA has to take up responsibility and get done all these things to prevent failures.