gmpkongress2013 session1 gdp kauer

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HC Compliance

September 26th, 2013 GDP Good Distribution Practice

September 26th, 2013

GDP Good Distribution Practice

The new EU guidelines and their implementation

Klaus Kauer

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HC Compliance


Agenda

Current GDP regulations and guidelines

What needs to be done by the pharmaceutical industry to be GDP compliant?

What do the new guidelines mean for logistics companies?

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FROM GMP to GDP

The major transformational trend for the Pharma / Healthcare Supply Chain is that GDP has been separated from but is still aligned with GMP (Good Manufacturing Practice). That means GDP becomes more important especially from the perspective of an auditor and or inspector.

It is of key importance that the quality and the integrity of the medicinal products is maintained during the entire supply chain from the manufacturer to the patient.

Todays distribution network for medicinal products is increasingly complex and involves many players. The revised guidelines, published today, lay down appropriate tools to assist wholesale distributors in conducting their activities and to prevent falsified medicines from entering the legal supply chain.

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GDP

Good Distribution Practice (GDP) regulates the distribution of healthcare products from the premises of the manufacturer to the end user and is therefore part of the entire quality assurance process. It ensures that products are consistently stored, transported and handled under suitable conditions as required by the marketing authorization or product specifications during all aspects of the distribution process.

Worldwide, there are more than 35 GDPs (e.g WHO and FDA/EU). These are more or less aligned, but some have specifics like e.g. Argentina, Brazil, Saudi Arabia, etc.

Regulatory bodies have become stricter regarding the fulfillment of the GDP regulations like e.g. Saudi Arabia (Statement of the SFDA): No shipment of pharmaceutical products imported to the Kingdom will be cleared if it was proved that they were transported in non-cooled containers or stored in such a way contrary to the conditions recommended.

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GDP Regulations I

Country Regulations WWW Link

EU Guidelines on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01) (as of 7 March 2013)

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2013:068:0001:0014:EN:PDF

WHO WHO Technical Report Series, No. 957, 2010 good distribution practices for pharmaceutical products

http://www.who.int/medicines/areas/quality_safety/quality_assurance/GoodDistributionPracticesTRS957Annex5.pdf

Model requirements for the storage and transport of time and temperature sensitive pharmaceutical products TRS No. 961, Annex 9 (2011)

http://whqlibdoc.who.int/trs/WHO_TRS_961_eng.pdf

USA 21 Code of Federal Regulations - Parts 210 and 211 (21CFR211.150)

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.150

21 Code of Federal Regulations 820 Medical Devices http://www.fda.gov/medicaldevices/deviceregulationandguidance/postmarketrequirements/qualitysystemsregulations/

USP (1083) Good Distribution PracticesSupply Chain Integrity http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/c1083.pdf

USP(1079) Good Storage and Shipping Practices for Drug Products

https://mc.usp.org/sites/default/files/documents/GeneralChapterPDFs/c1079%20USP36.pdf

Canada

Guidelines for Temperature Control of Drug Products during Storage and Transportation

http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/compli-conform/gmp-bpf/docs/GUI-0069-eng.pdf

Argentina Regulacin de la cadena de fro de los medicamentos. http://www.anmat.gov.ar/webanmat/Legislacion/Medicamentos/Ley_26492_cadena_frio.pdf

Brazil GMP and GDP Requirements - National Health Surveillance Agency (Anvisa)

http://portal.anvisa.gov.br/wps/content/anvisa+portal/anvisa/sala+de+imprensa/menu+-+noticias+anos/2013+noticias/consulta+publica+reune+normas+sobre+boas+praticas+de+fabricacao

Denmark Good manufacturing practice (GMP) and good distribution practice (GDP)

http://www.dkma.dk/en/topics/authorisation-and-supervision/company-authorisations-and-registrations/manufacture-and-import-of-medicines-and---ermediates/gdp-and-gmp

UK Guidance in the Transportation of Medicinal Products, ambient and refrigerated

http://www.mhra.gov.uk/home/groups/is-insp/documents/websiteresources/con137881.pdf

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GDP Regulations II Country Regulations WWW Link Ireland Medicinal Products (Prescription and Control of Supply) (Amendment)

Regulations 2007 http://www.dohc.ie/legislation/statutory_instruments/pdf/si20070201.pdf?direct=1%20

IMB Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medical Products and Active Substance

http://www.coolpack.com/admin/documents/Regulatory/Ireland/IND-003.01x.pdf

China Good Supply Practice for Pharmaceutical Products http://eng.sfda.gov.cn/WS03/CL0757/78507.html

Australia Australian code of good wholesaling practice for therapeutic goods for human use

http://www.tga.gov.au/pdf/manuf-cgwp-tg.pdf

Singapore GUIDANCE NOTES ON GOOD DISTRIBUTION PRACTICE http://www.hsa.gov.sg/publish/etc/medialib/hsa_library/health_products_regulation/gmp/files_1.Par.84852.File.dat/GUIDE-MQA-013-009.pdf%20

India GUIDELINES ON GOOD DISTRIBUTION PRACTICES FOR BIOLOGICAL PRODUCTS

http://cdsco.nic.in/GUIDELINES.pdf

GUIDELINES ON GOOD DISTRIBUTION PRACTICES FOR PHARMACEUTICAL PRODUCTS

http://www.cdsco.nic.in/GDP%20final%20draft%20for%20pharmaceutical%20products_09012013%20-%20for%20website.pdf

Saudi Arabia Food & Drug Authority Temperature Monitors Taiwan Precaution of on-site sampling for vaccine testing and sealing operation

(Draft) Romanian Directive Legislation Change - Control of temperature/humidity during transportation

Singapore Health Sciences Authority Guidance notes on GDP (Draft)

Czech GDP Guidelines: DIS-15 version 1 Monitoring and temperature control during storage and transport of medicinal products

GDP Guidelines: DIS-11 Guidelines for correct distribution practice of human medicinal products

Egypt Minister Decree for Wholesalers Circular No. 4/2009

Indonesia GMP Requirements on warehousing or distribution Pakistan Drug Act of 1976 PDA: PDA Technical Report TR 52 (Aug 2011) Guidance for Good Distribution

Practices (GDPs) for the Pharmaceutical Supply Chain

IATA: Perishable Cargo Regulations (PCR); Chapter 17 Air Transport Logistics for Time and Temperature Sensitive Healthcare Products

http://www.iata.org/whatwedo/cargo/pharma/Documents/time-and-temperature-label-faq.pdf

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Quality Management (Chapter 1)

Premises and Equipment (Chapter 3)

Documentation (Chapter 4)

Subcontractor Management (Chapter 7)

Transportation (Chapter 9)

New EU GDP Guide in general: Structure

Main Topics

1.Quality Management

2.Personnel //Training

3.Premises and Equipment

4.Documentation

5.Operations

6.Complaints, Returns, etc.

7.Outsourced Activities //Subcontractor Management

8.Self-Inspections

9.Transportation

10.Specific Provisions for Broker*

(* Not valid for a Transportation Company)

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GDP Requirements of the Pharmaceutical Industry

Chapter 3 Premises and Equipment Quality Technical Agreement between contract giver and contract acceptor (Contract / SLA /

QTA) for all qualified facilities

Chapter 7 - Subcontractor Management (outsourced activities) Agreement between contract giver and contract acceptor (Contract / SLA)

Any activity covered by GDP must be correctly defined, agreed and controlled.

Supplier audits should be performed prior to use (wherever possible)

Frequency of audits depends on the entire risk of service

Subcontractor is not allowed to pass service to a third party without contract giver approval

The performance of the subcontractor (including number of complaints, deviations, etc.) must be regularly monitored and reviewed, results must be documented (management by KPIs)

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GDP compliant Subcontractor Management

Subcontractor Management

Auditing

SLAs

Management by KPIs

Selection process

Main Topic

Sub-Topics

A documented management of outsourced activities / Subcontractor Management including selection process, contracts and written agreements (Service Level Agreements according to GDP requirements) must be in place

The selection of subcontractors is based on predefined roles and they shall be audited prior to use.

GDP related KPIs must be defined, integrated within the SLA, monitored and reviewed.

As part of the signed contract, Service Level Agreements according to GDP requirements must be signed by all service providers.

Subcontractors must be audited according to an audit schedule on a predefined basis in line with the entire risk of service.

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What needs to be done by the Pharmaceutical Industry to be GDP compliant? Temperature-controlled shipments

Investigation of temperature excursions

Equipment suitable for use

Written procedures and risk assessment of delivery routes

Use of harmonized temperature ranges and dedicated labels (Air Freight)

Use of qualified equipment only: Road: ATP certified and qualified trucks http://www.tuev-sued.de/uploads/images/1139221651472619300056/ATP-Info.pdf [Accord relatif

aux transports internationaux de denres prissables et aux engins spciaux utiliser pour ces transports]

Air: Use of qualified (according to their use) packaging units only (active as well as passive)

Ocean: Reefer Guides Hamburg Sd: http://www.hamburgsud-line.com/hsdg/media/sharedmedia/dokumente/brochures/Reefer_guide.pdf

Hapag Lloyd: http://www.hapag-lloyd.de/de/products_and_services/reefer_cargo_handling.html

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What do the new guidelines mean for logistics companies (LC)?

Chapter 1 - Quality Management A responsible person must be designated . He or she must be appropriately competent and

experience d as well as knowledgeable about and trained in GDP (job description must clearly define responsibility and authority to fulfill duties).

The quality management system as well as the quality objectives are within the responsibilities of senior management (management, review and monitoring) and must be reviewed at least once a year (quality report)

All activities must be clearly defined, fully documented, trained and systematically reviewed. A training system must be available, all personnel involved should be trained.

A CAPA process aligned risk management process (referring to ICHQ9) has to be established.

Risk management must ensure that the evaluation of risk to quality is based on scientific knowledge and experiences. Also, a change management must incorporat quality risk management principles. Significant changes must be validated.

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What do the new guidelines mean for LC II?

Chapter 2 - Personnel

Key person regarding quality and compliance must be addressed (duties and responsibilities). Furthermore, the key person must train personnel in all relevant aspects.

Job description for key positions including deputyship must be specified.

Personnel must maintain competence in GDP including periodic training. The effectiveness of training must be periodically assessed (at least once a year).

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What do the new guidelines mean for LC III?

Chapter 3 Premises and Equipment Focus on ALL temperature ranges (not 2C to 8C only)

Qualified facilities:

Initial mapping of the facility to specify the position of monitoring devices.

Equipment used to control or monitor the environment must be calibrated.

Appropriate alarm systems must be in place and regularly tested.

Planned maintenance should be in place for key equipment.

Processes for cleaning, preventive pest control must be available

The presence of food drink, smoking material or medicinal products for personal use is prohibited

In case a computerized system is brought into use, the system must be validated prior to use.

Refrigerated vehicles:

Equipment must be maintained and calibrated regularly (at least once a year).

Mapping of vehicles should be done taking into account seasonal variations.

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What do the new guidelines mean for LC IV?

Chapter 4 Documentation Good documentation constitutes an essential part of the quality system

Documentation must be approved, signed and dated by appropriately authorized persons as required (written in a language understood by personnel, i.e. clear, unambiguous and comprehensive to all personnel) .Training records must be available.

Suitable documentation which prevents errors from spoken communication must be available

Documents should be regularly reviewed and kept up to date. Version control should be applied to procedures.

A SOP System must be in place. In case a computerized document management system is used, validation is required.

Each employee should have access to all necessary documentation (SOP) for the task executed

Documents should be retained for the period of at least 5 years

If its not documented, its not done. If its not signed, approved and trained, its worthless.

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What do the new guidelines mean for LC V?

Chapter 5 Operation (Warehousing) The new guideline is more specific regarding the qualification of subcontractors.

Regarding warehousing the following topics are addressed: separation, destruction of products. NEW "FIFO" ("first in first out") has been replaced by "FEFO" ("first expired first out")

Chapter 6 - Complaints, Returns of goods, fakes, etc. (Warehousing) Everybody involved in the handling and distribution process must / shall be able to identify such

products to reduce the patient risk. (Topic behind: training of staff)

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What does the new guidelines mean for LC VI

Chapter 7 - Subcontractor Management Any activity covered by GDP must be correctly defined, agreed and controlled.

An approved and signed agreement//contract by both parties must be available, including clearly defined duties of each parties.

Supplier audits should be performed prior to use (where ever possible)

Frequency of audits should be done based on the entire risk of service

Subcontractor is not allowed to pass service to a third party without PA approval

The performance of the subcontractor (including number of complaints, deviations, etc.) must be regularly monitored and reviewed, results must be documented (management by KPIs)

Chapter 8 - Self inspection Internal audit needs to be done and an audit schedule must be available.

NEW, internal audits can be done by third parties as well.

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Specific GDP Requirements of the PI III

Chapter 9 Transportation Mandatory use of qualified equipment and vehicles

Temperature conditions must be maintained within acceptable limits during the whole transport

Temperature monitoring equipment must be calibrated at regular intervals

A risk-based approach should be utilized when transportation is planned

A procedure must be in place for managing temperature deviations

Maintenance of used vehicles must be clearly defined within a procedure, records must be available for all used vehicles, including cleaning and safety precautions.

For the intermediate storage, requirements are the same as for storage. (Chapter 3) Medicinal product should be transported in accordance with the storage conditions indicated on the packaging information.

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Summary

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GDP compliant Quality Management

Quality Management

Document Management /

SOPs

Training & Job Description

Risk & Change

Management

Deviation Management

QM Handbook-

Report

Main Topic

Sub-Topics

A global GDP-compliant quality management system must be established, including a QM handbook. Quality and compliance-related goals according to key processes must be defined and reviewed at least once a year, resulting in a QM annual report.

A quality management handbook must be established describing all key processes. Quality objectives are within the responsibilities of senior management (management, review and monitoring) and must be reviewed at least once a year (quality report).

A document management system / process must be in place. All quality / compliance- related documents like SOPs, WIs, etc. must be approved, signed and dated by authorized persons. Documents must be archived for a minimum timeframe of five years.

The organization must establish a documented deviation management (incident handling) process including a CAPA (corrective and preventive action) process, aligned with the risk management process (referring to ICHQ9).

Key person regarding quality and compliance must be addressed (duties and responsibilities) as well as personal training. Maintain competence in GDP including periodic training. The effectiveness of training must be periodically (min. once a year) assessed.

A documented change and risk management process must be in place. For quality-relevant changes risk assessment must be done, therefore significant changes must be validated and approved by the related quality organization.

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GDP compliant Qualification & Validation processes

Qualification & Validation

V. of Processes

V. of IT Systems

Q. of Facilities

Q. of Service-providers

Main Topic

Sub-Topics All service providers must be qualified according to predefined roles in line with the GDP requirements.

Processes regarding qualification and validation must be defined and rolled out.

Storage facilities and used equipment for temperature-controlled products must be qualified (authorization, certification and compliance-audit prior to use).

The potential risk of computerized systems must be evaluated and systems must be validated depending on the result of the RA (according to predefined roles inline with e.g.: EU GMP Annex 11 and US 21CFR Part11)

Process validation (e.g.: transport validation) must be defined

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GDP Compliance Process Map

Quality Management

Qualification & Validation

Subcontractor Management

Document Management /

SOPs

Training & Job Description

Risk & Change Management

V. of Processes Auditing

SLAs V. of IT Systems

Management by KPIs Q. of Facilities

Selection-process

Q. of Service-providers

Deviation Management

QM Handbook,- Report

Main Topics

Sub-Topics

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In a nutshell

Outsourced activities must be correctly defined, service level agreement must be signed by all

parties involved

Regularly Business Review Meetings (KPI review) must be scheduled

Rules for communication must be defined and established (claims, deviations, changes, etc.)

All GDP-related processes must be documented, approved, signed , trained and documented

The maintenance of a quality system setting out responsibilities, processes and risk management

principles must be in place

All staff handling pharmaceutical shipments must be trained.

Adequate premises, installations and equipment must fulfill proper requirements for storage and

distribution of products

Appropriate management of complaints, returns must be in place

Rules for transport must be defined particularly to keep the product integrity and to ensure that

temperature conditions are maintained within acceptable limits during transport;

The revised guidelines are entered into force, September 08th, 2013.

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Real-Time Visibility & Intervention Capabilities with PanCool

GDP Trucking

Cool rooms / GDP

Defined process for de-consolidation or re-

icing Full control on OCN and with

selected cariers

PanCool Set-up

Real-time Visibility

Manufacturer

GMP

PanCoE /

GDP Hub

Approved reefer truck

Approved reefer truck

Airport / Terminal / Tarmac / Loading

Airport / Terminal / Tarmac / Loading

PanCoE / Distribution Center / GDP Hub

Consignee

Qualified plane Full control on OCN and with selected

cariers

GDP Trucking

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Global HC Compliance Support

Process design

Appoval of Master SOP

Quality Agreement

Support of validation and qualification activities

Train and support the process related Quality Persons

Compliance topics in QBR / MBR

THANK YOU FOR YOUR ATTENTION! QUESTIONS?

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Klaus Kauer

Industry Vertical Healthcare

VP, Corporate IV Healthcare Compliance Manager

Panalpina Management Ltd., Corporate Head Office,

The Squaire 13, Am Flughafen, 60549 Frankfurt am Main

Phone: +49 69 698 678 283

Mobile: +49 172 1850 728

E-Mail: [email protected]

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