Quality Manual Version 7.2 ENG – August, 2017 1 / 10

POLYPLUS-TRANSFECTION®

QUALITY MANUAL

Version # Version motive Author Checked by Approved by Application date

7.1 Update of the document C. Wartel-Weill G. Guérin-Peyrou M. Bloomfield September 1st, 2015

7.2 Upgrade of the document

V. Bergmann C. Wartel-Weill K. Wilking August 29, 2017

Quality Manual Version 7.2 ENG – August, 2017 2 / 10

Polyplus-transfection® is focused on developing innovative solutions for delivery of biomolecules. The company has been marketing its transfection reagents worldwide since 2001 and is reinvesting most of its revenues in research and development. Our mission is to continuously develop and supply innovative delivery solutions, with a concomitant outstanding technical and scientific support to our customers. Transfection is the process of introducing genetic material, such as DNA or small interfering RNA into cells. This process facilitates cellular uptake of biomolecules and makes it possible for such biomolecules to be delivered into the cells for research or therapeutic purposes. The Strasbourg-based company is recognized as a leading innovator in the transfection market, with the ISO 9001:2015 certification, exclusive licenses from the CNRS and numerous patent applications pending. Polyplus-transfection®’s R&D department has well-established partnerships with leading biotechnology and pharmaceutical companies.

Polyplus-transfection® has been selling its products and services through an international distribution network since 2001. End-customers include biotechnology companies, research and pharmaceutical laboratories.

Polyplus-transfection® offers high quality consultancy, personalized scientific support and expertise in regulatory affairs related to the use of its reagents in clinical trials. Phases I/II/III clinical trials are underway in Europe and USA using GMP-compliant (Good Manufacturing Practice) reagents from Polyplus-transfection®.

Polyplus-transfection®, dedicated to the intracellular delivery of biomolecules

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Based near Strasbourg in France, Polyplus-transfection® is a growing company with a staff of 35 employees. The organization of the company is structured according to the following organizational chart: Key figures for the year 2016:

10671

final products sold

40

countries where

product are marketed

5.47

M€ of sales revenue

0.24

% of customer complaints for products sold

Our Organization

CEO & Chairman

CFO

Sales Administration

Human Ressources

Accounting & Financial

Department

Administration & General Services

Management

Business Directors

Business Development

Manager

Legal Department

Custom Products

& Services

CSO

Production

Quality Control

Director of Marketing & Tech Support

R&D: New Product

Development

Operational Marketing &

Communication

Technical Support

HSE Manager

Quality Manager

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Polyplus-Transfection® is fully committed to Quality and Environmental approaches that define and ensure specific internal requirements are translated into policies and objectives.

Our Quality and Environmental commitments

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Since 2002, Polyplus-transfection® is certified ISO 9001 for all its processes by the AFNOR organism. This certification ensures that the company was founded and continue to develop itself on a robust Quality Management System. Over time, the company has maintained and improved the control of its processes thanks to a constant improvement strategy. In recognition of this commitment, Polyplus-transfection® was certified ISO 9001:2015 version (certificate below) during a follow-up audit in October 2016.

With the ISO 9001:2015 certification, the company sustainably meets the needs of customers thanks to a process control and to the fulfilment of its engagements, thereby ensuring consistent and high-quality product and customer service. This certificate has been obtained thanks to the implementation of the Quality Management System described below.

Our Certifications

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All ongoing activities in the company are depicted in the adjacent Quality House scheme:

• The management commitment and the customer-oriented strategy constitute the roof of the Quality House. They both provide the rules, the course of action and the direction to follow.

• The management commitment and the customer-oriented strategy are based on several pillars: provide high quality products, ensure employee safety, actively listen to customer needs, and finally run an eco-friendly business.

• The processes and activities performed by the company constitute the basis of the Quality House. Process control, staff training, control of records, and evidence-based decision making are fundamental in meeting the requirements defined by Polyplus-transfection®.

The development, implementation, fulfillment and the continuous improvement of this quality organization ensure the continuity in the activities/work and customer satisfaction.

Our Quality Management System

Our Organization, « Quality House »

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Polyplus-transfection® has chosen to use a process approach during the development, the implementation and the improvement stages of the Quality Management System. The process map used by the company is described below:

- Management process: defines the quality policy and objectives, areas for improvement, as well as

the Quality Management System controls. - Realization process: represents all processes that take part in the realization of the product. - Means process: provides the means needed to run the realization process.

In addition to this « Process Map », the company uses « Process Sheets ». These Process Sheets each summarize actors and pilot(s), activities performed, associated documentation, links with the suppliers (internal/external) using SIPOC, indicators and specifications, and finally associated risks and opportunities. These Process Sheets are updated at least once a year during the process reviews. This process approach allows the company to manage its activities and to generate benefits, while monitoring the interaction and interdependency between processes.

A process approach

Our Quality Management System

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The Quality Management System control and the continued improvement of Polyplus-transfection® are guaranteed by the implementation of several monitoring elements defined below:

Internal audit Alike the external audit, this annual internal exam is accomplished for each process of the company by a certified internal auditor.

Deviation management/CAPA Non-Conformities/Deviations detected by the company are recorded. A root cause analysis of the origins of these deviations is realized. Then, preventive/corrective actions are defined to avoid its recurrence. Finally, a follow-up of the corrective/preventive action efficiency is made.

External audit Accomplished by a certifying body (AFNOR), it is a methodic, independent and documented annual exam. It provides proofs of our Quality Management System organization and of its objective evaluation.

Management review Planned at the beginning of the year after the process reviews, this review takes place with the management team and all the process pilots. Performance and needs are identified and assessed during these reviews. Report is communicated to all employees of the company.

Process review Achieved by pilots and actors of processes, this annual review is used to evaluate the performance, to follow-up on the planned actions, to define needs and resources, as well as to update the internal documentation. Issued reports are communicated to all employees of the company.

Customer complaints Customer complaints are tracked by the company. They are assessed and generate short- and medium-term actions. Medium-term actions are handled following the deviation process. A follow-up of all the implemented actions and their efficacy is performed.

Performance indicators To control the activities, robust, sensitive, clear and relevant performance indicators are implemented. A follow-up of these indicators is summarized in a dashboard. The dashboard is frequently revised.

Our Quality Management System

Our control system

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To ensure reproducibility in its activities and the fulfillment of its requirements, Polyplus-transfection® relies on a number of data/information. Generated documents are controlled thanks to a proof reading/approbation system and are managed according to a pyramidal organization. The documentation pyramid implemented by the company is described below:

The main procedures

Control of documents: PR GE 01 and PR GE 05 Control of records: PR GE 03 Internal audits: PR GE 06 Control of non-conforming products: PR GE 07 Control of deviations: PR GE 07 Control of modifications: PR GE 09 Control of customer complaints: PR ST 03

The Quality Manual

It defines the orientation of our quality approach and it describes the general organization of the company. Regularly updated, this document is managed by the quality service and proofread by the direction. The Quality Manual is communicated to the employees according to internal requirements, and communicated to stakeholders to inform them of our commitments.

Our Quality Management System

A controlled documentation system