Meeting daily compliance in PharmaOperations - Hess … Meeting daily compliance in... · Meeting daily compliance in PharmaOperations. ... FDA cites violations at three Novartis

Dr. Hess Interim ManagementUmfassende Kompetenz in Logistik und Produktion

SKMF Spring Event 2012

Dr. Peter Hess

Meeting daily compliance in

Pharma Operations


Themenübersicht

� Compliance Framework

� GMP

� Activities and compliance documentation in a

production plant

� Compliance preconditions

� «The way» to compliance

� Intangible assets and value creation

� The missink link


Pharma Compliance in the Press

� Reuters, Dec 6, 2011: FDA cites violations at three Novartis plants

� (Reuters) - Drug regulators cited Novartis AG for "significant violations" of manufacturing regulations at its three generic drug plants in the United States and Canada, several of which were repeat offenses.

� "We are concerned that your firm lacks process understanding to consistently manufacture", FDA wrote in the letter dated November 18.

� US department of Health & Services/FDA; Jan 8 2012: Novartis is voluntarily recalling all lots of two products / Novartis commitment to quality� Novartis Consumer Health, Inc. (NCH) announced today that it is voluntarily recalling all lots

of select bottle packaging configurations of Excedrin® and NoDoz® products … because the products may contain stray tablets, capsules, or caplets from other Novartis products, or contain broken or chipped tablets.

� The Novartis Group is fully committed to ensuring the quality, safety and integrity of its products. All Novartis Group companies have a clear commitment to patients and Health Authorities to ensure high quality standards for all our products and services.

� Pharma Manufacturing Newsletter | February 6, 2012: FDA report shows deep problems at closed Novartis Consumer Health plant.� Novartis has set aside $120 million to address shortcomings at the plant and CEO Joseph

Jimenez has told the investment community he is confident the plant will reopen mid-year.


Compliance Framework in the Pharma Industry

� Ultimate goals of compliance: Safeguarding the health of the patient as well as

producing good quality medicine, medical devices or active pharmaceutical products.

� cGMP (Current Good Manufacturing Practice): Main mandatory regulation for Pharma Industry anchored in the US federal Food, Drug, and Cosmetic (FD&C) Act and EudraLex Volume 4 in EU.

� "GMP" - A set of principles and procedures which, when followed by manufacturers for therapeutic goods, helps ensure that the products manufactured will have the required quality.

� A basic tenet of cGMP is that quality must be built into each batch of product during all stages of the manufacturing process.

� cGMP is that part of Quality Assurance aimed at ensuring that products are consistently manufactured to a quality appropriate to their intended use

� Compliance Monitoring & Enforcement: Inspections performed by national Regulatory Agencies like CH: Swissmedic, US: FDA, EU: DG Health & Consumers). Regulatory agencies are authorized to conduct unannounced inspections at any time the firms are open for business.


GMP covers….

� ALL aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff.

� Documents: Detailed, written procedures are essential for each process that could affect the quality of the finished product.

� Document Management: There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made.

� Quality management system (QMS): Each company has to create own individual QMS which integrates cGMP requeirements but covers and integrates many other (national) regulations, quidelines, internal policies.

� Qualification requirements (§ 211.25 ): Each person engaged or responsible for supervising in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions.

Management approach: «The parameters and requirements to achieve compliance are given, let’s do it «

– How do companies manage all that know-how

– How can all employees know at any time what and how to do

– Responsibilities and


Compliance Management Systems

But: is that all…. ?


Overview activities in production plant

� Synthesis of final Product (API) : Several chemical stages required

� Products are manufactured in campaigns with multiple product lines configured to operate simultaneously.

� Parallel to the production: cleaning (product change), maintenance (repair, qualification, calibration).

� Summary: Dozens of different activities take placeat the same time.

Handling

• Sampling

• dispensing

• weighing of materials

Loading

• Solvents

• reagents

• intermediates

Process

• chemical reaction step

Work Up

• quench

• evaporation

• filtration

• extraction/

• phase separation

Isolation

• crystallisation

• filtration

• centrifugation

• drying

• milling

• sieving

• blending

API

KI

IP1

SM1 SM2

IP2

SM3

A single stage


Compliance: Overview important documents

• Policies

• SOP

• Specifications

• Master Formula Record

• Batch MR

• Manuals

• Master plans/ files

• Validation protocols

• Forms and Formats

• Records

Buildings

Infrastructure

Process Equipment

Control Systems

Documentation

Hygiene

Manufacturing

Utilities

Tank Farm

Warehouse

QC

Personel

Regulated Areas Documentation

• Policies

• SOP

• Specifications

• Master Formula Record

• Batch MR

• Manuals

• Master plans/ files

• Validation protocols

• Forms and Formats

• Records

Activities

Policies

SOP

Specifications

MFR (Master

Formula Record)

Batch MR

Manuals

Master plans/ files

Validation

protocols

Forms

Security & Safety

Process work

Monitoring

Cleaning

Validation

Calibration

Qualification

Sampling

Staff Training

How can all employees know at any time what and how to do?


Compliance Preconditions

GMP

Compliance

Zero Error Culture Operational Excellence

Something missing ?

Experience, Further learning

Training on the job, SOP’s, Practical GMP-raining

GMP Theory, Company Guidelines, Education

Willngness

Ability

Knowledge

Information

How can a plant manager guarantee

and account for compliance relying on

many Individuals ?

How to achieve compliance?

Compliance “happens” all the time,

everywhere with every action:

All management

& staff levels

Novartis non-compliance??


The «way» to compliance

«Complience Rules»

???

Enforcement?

Empowerment?

Control ?

Trust ?

«The Way»

«The Goal»




?

«The Way»




?

«The Way»




?

«The Way»


Intangible assets and value creation

Goal of Knowledge Management*)«A systematic approach to find, understand, share and use knowledge to cretae value»

Pharmaceutical industryKnowledge based organizationswith focus on operational excellence(= processes, quality & costs) usebest practice by sharing knowledge

Individual / intangible Assets

= Knowledge and Abilities of the managers, middle managers and frontline employees

*) Carla O'dell, C. Jackson Grayson, If Only We Knew What We Know, pioneers in Knowledge Management

Leadership

The true foundation of value creation are

the intangible assets of the companies=

The ability to craete value depends not on written

proceders and quiedelines, but on the willingens and

motivation of individuals to focus on their daily

work, to reach their daily goals and all compliance

requierements

Willingness and

Motivation

Value Creation


Summary: The missing link

GMP

Compliance

Zero Defect Culture Operational Excellence

Skills, Behavior, Cultur

Experience, Learning

Training on the job, SOP’s,Practical Training

Company Guidelines, Education, GMP Theory,

Motivation

Ability

Knowledge

Information

The ability to craete value depends not on

written proceders and quiedelines, but on the

willingness of individuals to focus on their

daily work, to reach their daily goals and all

compliance requierements

The ultimate driver for business success

i.e. compliance is to transform knowledge

and ability into willingness and motivation

of each individual and his performance


The most ancient and simple compliance approach !

Epicurus, 341-270 BC, is one of the well known

writers of antiquity.

The central point of his thinking was linked to the

question:

On what relies the happiness of the wise man?

Epicurus replies (fully in the meaning of GMP-

compliance):

The wise man arranges his life according to rules

to relieve him from of fear, pain and desire


Vielen Dank !

Fragen?