Healthcare Good Distribution Practice...

HealthcareGood Distribution Practice (GDP)

The place to go for free supply chain advice1

The role of the MHRA

• Ensuring that medicines and medical devices work, and are acceptably safe.

• No product is risk-free. Underpinning all their work lie robust and fact-based judgements to ensure that the benefits to patients and the public justify the risks.

• To keep watch over medicines and devices, and take any necessary action to protect the public promptly if there is a problem.

• They aim to make as much information as possible publicly available.

• Enable greater access to products, and the timely introduction of innovative treatments and technologies that benefit patients and the public.

• Encourage everyone - the public and healthcare professionals as well as the industry - to tell them about any problems with a medicine or medical device, so that we can investigate and take any necessary action

The powers of the MHRA

Keeping updated: sign up for MHRA email alerts

• Revoked authorisations

• New authorisations and register of medicines manufacturers, importers and suppliers

• Devices and medicines alerts

• Newly granted Marketing Authorisations (MA)

• News

• Help & advice

• Enter premises & inspect goods

• Request records and take copies

• Seize and/or detain suspect records and/or goods which may be required as evidence in proceedings for an offence

• Test purchases

• Prohibit the supply of goods considered to be unsafe

• Recall Notices (DMRC)

• Suspend or revoke authorisations

• Remove an RP from the register!

February 9, 2016, the Delegated Act on safety features was

published. EU FMD specifically outlines how the EU FMD

contains three major government requirements:

• SERIALIZATION (Must happen at the secondary or

saleable-unit level in Europe)

• VERIFICATION AND SAFETY FEATURES (2D barcode,

Anti-tampering technologies)

• COMPLIANCE REPORTING

European Medicines Verification Organization (EMVO) oversees the following:

• The European hub (Connect and exchange data with multiple national systems, maintain master data and pack status as product moves through the supply chain)

• A blueprint system offered by EMVO-approved vendors (available to reduce time, risk, and cost)

• Service providers

• Service-level agreements with national authorities

Launched an online portal for pharmaceutical companies, offers guidance documents for on boarders to ensure that their systems are compliant https://www.emvo-medicines.eu/announcements/

Good Distribution Practiceof Medicinal Products For Human Use

2001/83/EC Medicines Directive 2011/62/EU Falsified Medicines Directive 2013/C 343/01 GDP Guidelines

What is in the Guidelines?2013/C 343/01

1: Quality Management

2: Personnel

3: Premises & Equipment

4: Documentation

5: Operations

6: Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Product Recalls

7: Outsourced Activity

8: Self-Inspections

9: Transportation

10: Specific Provisions for Brokers

1.1: Principal

Wholesale distributors must maintain a quality system setting out responsibilities, processes and risk management principles in relation to their activities.

Quality Management - 2013/C 343/01Chapter 1

• All distribution activities should be clearly defined and systematically reviewed

• All critical steps of distribution processes and significant changes should be justified and where relevant validated

• The quality system is the responsibility of the organisation’s management and requires their leadership and active participation and should be supported by staff commitment

Quality Management2013/C 343/01

M.A.R.I.O.

Process Approach To Quality System

Activity

Management

Resources

Input Output

QUALITY MANUAL (MASTER FILE) – WHAT YOU DO!

• Company Details

• Scope of Quality System

• Exclusions

• *Quality Objectives (must be Specific, Measurable, Achievable, Relevant, Timely + Evaluated, Reviewed)

• Process Flowchart

• An Organisational Chart

Quality System: Sample of Contents

• Management Responsibility

• Management of outsourced activities

• Management Review & Monitoring

• Quality Risk Management

PROCEDURE MANUAL (SOPS) – HOW YOU DO IT!

• Standard Operating Procedures

Quality System: Contents

• SOP NUMBER

• VERSION

• DOCUMENT TITLE

• PAGE NUMBER

• DATE

• PROCEDURE FLOWCHART*

• SCOPE

• PURPOSE (WHY)

• RESPONSIBILITIES

• DEFINITIONS

• PROCEDURE – SAY WHAT YOU DO, DO WHAT YOU SAY!

• ASSOCIATED DOCUMENTS

• PROCESS OWNER AND RP APPROVALS

Quality System: Contents

Sample of an Organisation’s Process Flowchart

Marketing Dept:

Quotation

Purchasing Dept:

Place Purchase

Order with Supplier

Customer places

Warehouse:

Goods received,

checked and

entered onto stock

Customer

Enquiry

Customer Service:

Process Customer

Warehouse:

Pick, sort, pack &

despatch goods

Finance Dept

Raise & send

invoice to Customer

Post Market Activity

Complaints, Investigations

Customer Feedback

Documents:

Quality Manual, SOPs, uncompleted Registers and Forms

Records:

Entries into Forms & Records, collected data

Example:

The form used to create a purchase order is a document, once purchase order has been completed and sent to the supplier, it becomes a record.

Documents and records can be review or check by staff but can only be approved by the RP!

Quality Systems – Document & Record Control: Clause 4.2

Quality system structure

PDCA: Plan-Do-Check-ActChange Management

• Objective

• Activities

• Resources

• Risks

• Documentation

• Control

• Analyse review

• Change

• Maintain effectiveness

• Deploy as per plan

• Review

• Re-assess risks

• Measure

• Monitor effectiveness

Quality Risk Management: Clause 1.5

“A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle”

The word ‘risk’ is mentioned 27 times in the Guidelines.

26/07/2017 info@pharmacyconsulting.co.uk 17

Analyse Risk

Assess Risk

Control Risk

Review Risk

Risk Management

Risk Rating

Low or Broadly Acceptable RiskThe probability and/or severity of the risk are so low that the risk is negligible.

Medium RiskThe risks within this region should be reduced as far as possible

High or “Not acceptable risk” The probability and/severity of these hazards should be reduced to Low or broadly Acceptable(for patient health, these risks must be reduced

A Medic ine Dist r ibutor ’s Warehouse Management System sof twarei s no longer able to cope wi th the increase of s tock and stockmovements so new sof tware wi l l need to be sourced and insta l led.What r isks could be cons idered?

Risk Management Example

Hazard Cause Harm Risk Rating Risk ControlResidual

Incorrect or incomplete data transferred from existing system to new one

Systems incompatible OrErrors in manual entry of legacy data

Historical data could be lost or incorrect

Ensure compatibility between systems and validated prior to implantation. Check and test manually transferred data and test

The new system does not do everything that the old system does

Not obtaining userinterface specifications (UIS) prior to installation

Software does not enable key functions i.e.:Unable to track & trace stock, process sale & purchase orders

Included all key personnel when deciding specifications and functionality of new software

Medium

Responsibilities of the RP: Clause 2.2 of Guidelines

• Should fulfil their responsibilities personally and should be continuously contactable –Duties may be delegated but not the responsibility

• A written job description or Technical Agreement defining authority

• Defined authority, resources and responsibility

• Carry out duties in a way that the wholesale distributor can demonstrate GDP compliance

• Ensure the quality management system is implemented and maintained

• Managing authorised activities and the accuracy of records

• Ensure that training programmes are implemented and maintained

• Recalls

• Ensure relevant complaints are handled effectively

• Supplier/Customer approvals

• Subcontracted activity approval

• Self-inspections and CAPAs

• Records of delegated activities

• Disposition of non-conforming/returned product

• Approval of returned products

• National Law updates are implemented

Personnel: Clauses 2.3, 2.4 & 2.5

• Adequate personnel dependant on volume & scope of activities

• Roles, responsibilities, and inter-relationships defined

• Written job descriptions

• Trained

• COMPETENT!

• Appropriate Hygiene measures

Premises: Clause 3

• Suitable & adequate

• Secure – security & cameras

• Structurally sound

Essential standards for a warehouse

• Medicines stored in segregated, clearly marked areas

• Authorised personnel only/access control

• Clearly defined quarantine locations

• Protection from prevailing weather conditions

• Goods-In/Out separation – logic workflows

• Pest Control (preventive)

• House Keeping programme & records

• No food, drinks, tobacco, personal medicinal products

Essential standards for a warehouse: temperature and environmental control Clause 3.2.1

What is wrong with this picture?

Is this a medicines fridge or meat fridge?

Which temperature is correct?

What is wrong with this fridge?!

• No air circulation

• Goods blocking fan

• Goods in Goods out mixed

What to look for in an

ideal fridge: • External temperature

reading/alarm• Lockable• Wire shelving enables

air flow• Ensure that there is

ample space around the fridge to allow good ambient air flow.

Essential Standards for a Warehouse Temperature & Environmental Control: Fridge Mapping

Essential Standards for a WarehouseEquipment: Clause 3.3

• Validated/ Verified

• Maintained

• Calibrated

• Alarmed

• Repaired

• Maintenance is planned & recorded

Computerised Systems: Clause 3.3.1

• Validated or Verified

• Written detailed description of the system

• Up to date, principles, objectives, security measures,

◦ system scope & main features

• Diagrams where appropriate

• Data security

• Repaired

• Procedures for system failure

Essential Standards for a WarehouseStorage: Clause 5.5

• Protect medicines

• Stock rotation (FEFO)

• Handled/Stored carefully

• Removal of short shelf life stock

• Regular inventory

• Investigation of stock irregularities

Qualification of Suppliers/Customers: Clauses 5.2 & 5.3

• Are the customers/suppliers who they say they are?• How can we ensure this?

• GPs, WDA(H), Marketing Authorisation –full copy with notarised translation (where required)

• EudraGMP GDP Compliance Certificate (specifically for suppliers)

• Appropriate qualification (questionnaire/audit)

• ‘Due diligence’ checks –websites/references/additional certification

http://eudragmdp.ema.europa.eu/inspections/logonGeneralPublic.do

Compliance with Good Distribution Practice (Suppliers

only):

“A certificate of Good Distribution Practice (GDP) is

issued to a wholesale distributor by the national

competent authority that carried out an inspection if the

outcome of the inspection confirms that the wholesale

distributor complies with Good Distribution Practice, as

provided by European Union legislation. If the outcome of

the inspection is that the wholesale Distributor does not

comply a statement of non-compliance may be entered

into EudraGMDP. GDP certificates and statements of

non-compliance may be issued to wholesale distributors

of medicinal products and distributors of active

substances.”

Complaints: Clause 6.2

• Distinction between product and distribution issues

• Inform manufacturer or marketing authorisation holder

• Investigate distribution issues

• Appoint a member of staff and allocate sufficient personnel

• Follow up actions including CAPA

• RP review and sign off

Returns: Clause 6.3

• Written Procedure

• Is it damaged?

• How long has it been out of your control?

• Where has it been?

• How has it been stored?

• What temperature has it been stored/transported at?

• Can you prove it?

• RP approval & signature

Falsified Medicinal Products: Clause 6.4

• Any part of a medicine, packaging or paperwork – not just counterfeit

• Written procedure

• Inform MA holder/RP/MHRA

• Segregate immediately

• Document and retain records

Reports can be made for all medicines including vaccines, blood factors and

immunoglobulins, herbal medicines and homeopathic remedies, and all medical devices

Medicinal product recall: Clause 6.5

• Capable of being initiated at any time

• Follow the instructions of the recall

• Record recall operation at the time & available to the competent authority

• Records of distribution readily accessible (traceability)

• Recall progress recorded for final report

• Evaluate effectiveness of recall procedure (dummy recalls)

• Negative recall records

Outsourced activity: Chapter 7

•WRITE IT DOWN!

•Whom did you talk to?

•When did you talk to them?

•Where were they?

•What process were they doing?

•What documents & records did you review (both paper & electronic)

•What did you see & hear (observe)

•What were your findings?

•Your notes should be legible and are retained for future reference

Non-conformity

Minor Non-conformities:

• A “one off” incident

• Human error

• Minimal or no risk to product or service

Example: The housekeeping records were found not to have been completed for one day, all the other records were found to be complete (procedure **/Clause 3.2)

Major Non-conformities:

• Systemic, repeated minor incidents relating to the same clause of the standard, directive or guidelines

• A break-down in the effectiveness of the Quality System – i.e.: not following the approved written procedures

• A single or multiple non-conformities that could have detrimental effect on products or service (patient safety)

Example: Following a report that a product had failed during use, the written

procedure and the requirement for reporting product failure was not applied (procedure ***/Clause 6.2)

What is a non-conformity?• Not meeting the specific requirements of a standard,

directive or guidelinesOr

• Not following the approved written procedures

Follow-up

• Capable of being initiated at any time

• Follow the instructions of the recall

• Record recall operation at the time & available to the competent authority

• Records of distribution readily accessible (traceability)

• Recall progress recorded for final report

• Evaluate effectiveness of recall procedure (dummy recalls)

• Negative recall records

Transportation: Chapter 9

“STORAGE CONDITIONS MUST BE MAINTAINED DURING TRANSPORTATION”

• WDA(H) holder must protect products from adulteration

• Transport within the temperature range indicated on the packaging

• Report excursions

• Inform contract providers of storage requirements

• Use dedicated vehicles where possible

• Risk assess the delivery routes

• Validate the route/methods to be used

Introducing for Export

What do you need on your license:

◦ 1.3 Without Marketing Authorisation in EEA not for use in EEA

◦ 2.4 Export

◦ 4.7 Importing from outside EEA to send outside the EEA

◦ If the origin is outside the EEA but bought from an EEA provider it’s still a ‘special’.

◦ If buying ‘specials’ in EEA and exporting you don’t need 4.7 on your license.

Brokers: Chapter 10

Specif ic provisions for brokers

“A broker is a person involved in act iv i t ies in re lat ion to the sale or purchase of medic inal products, except for wholesale distr ibut ion, that do not include physical handl ing and that consist of negot iat ing independent ly and on behalf of another legal or natural person”

Self Inspection: Clause 8.2

Self-inspection: objectives

• To assess conformity to statutory, regulatory and contractual requirements

• Evaluate the effectiveness of the Quality System

• Identification of areas of improvement

Self Inspections focus on the RP not the Director

Scope and Plan for self-audits to cover compliance with all aspects of Good Distribution Practice

Culture – RP dispute with directors

Lack of details on the Qualification of Suppliers/Customers

No detailed bona fides checked on Export Customers

No reassurance that licence suspensions and revocations would be captured and acted on in a timely manner.

RP –what activities are conducted by the RP –procurement process

CPD for RP

GDP Training- Competence check of Directors

Audit Evidence (objective evidence)

• Review related documents and records and record document references and Issue/Review numbers

Keep the audit fact/evidence based

Review documents

Plan audit

Summary Report Nonconformity Report(s)

Corrective Action(s)

Review of Corrective Actions

Audit sequence

The Inspection: What to Expect

• Application + fee

• Standard operating procedures

• Technical agreements

• On-site or contract warehouse

• Site for administration

• Internal or contract RP

• 90 days for inspection 1

• 9 months for inspection 2

• Future inspections are based on your compliance at the time of your 9 month inspection – The more compliant you are, the longer between inspections.

BE PREPARED FOR A CANCELLATION!

Future inspections are based on your compliance at the time of your 9 month inspection – The more compliant you are, the longer between inspections.

• Compliancy leads to a positive GDP Compliance report

• Up to 4 years before your next inspection

The Inspection: What to Expect

• Quality of product and service to ensure public safety

• Risk assessment, both proactive and reactive (including Change Management)

• Validation relating to the introduction of the Falsified Medicines Directive

• Calibration

• Records – keeping, maintaining & archive retrieval (Records are to be retained for a minimum of 5 years –including personnel records)

• Evidence of compliance

If it hasn’t been recorded – it hasn’t happened!

Inspectors like written records

Inspectors do not to look for deviations – they will

jump out while trying to find evidence of compliance

Feedback from MHRA inspections

•Review all your QTAs – even if ongoing, follow through/review

•TAs not signed by both parties and often expired

•No formal assessment of the arrangements for the safe and secure transport of products to customers

•Risk assessment of transport did not cover all arrangements

•No process in place for controlling outsourced activities

•Regularly evaluating the effectiveness of the arrangements for product recall

For more details on any of these topics, please contact us at: silverback@idrislogistics.co.uk

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