Www.AllianceBiosciences.com Malcolm Barth, Ph.D. Marian Downing, RBP, CBSP, SM(NRCM) Ryan Burnette, Ph.D., Director Biosafety Program Management Refresher

www.AllianceBiosciences.com

Alliance BiosciencesMalcolm Barth, Ph.D.

Marian Downing, RBP, CBSP, SM(NRCM)Ryan Burnette, Ph.D., Director

Biosafety Program Management Refresher Course


What does a BSO have to know?◦ No correct answer – “It depends”◦ ABSA’s definition of a Biosafety Officer is outlined in the NRCM

(National Registry of Certified Microbiologists) task list for Biological Safety

◦ Some of these tasks may not apply to your institution, e.g., BSC certification (but you need to know the basics) How to pack and ship infectious materials (you may have a trained

shipping group) Select Agent regulations

Definition of a BSO


Develops, implements, maintains and monitors biosafety programs, policies and procedures◦ Goal is to reduce/eliminate

exposure to biological hazards Provides recommendations for

use/storage/disposal of infectious waste in accordance with applicable laws

Manages/performs laboratory inspections

Develops and delivers biosafety training

May supervise and develop staff

Reviews/advises on research protocols for rDNA, human-sourced materials, Select Agents/Toxins

Sits on various committees: IBC, IACUC, IRB, Occupational Health, etc.

Responds/investigates spills and accidental exposures

Finds time for personal professional development!

In General, a BSO:


A BSO is required if:◦ There is rDNA ongoing at an institution, and◦ There is large scale (>10 Liters) of recombinant work, or◦ There is BSL-3 work with rDNA materials

Select Agent regulations do not specify a “BSO”, but leave the door open for a PI to potentially fulfill all the registration requirements.

Some institutions – the BSO does very little beyond reviewing IBC research proposals and lab inspections.

Other institutions – the bulk of the IBC operational issues are handled by a Research Compliance Group.

BSO



Management commitment to safety, which may be classified as including:◦ Prioritization of safety over production (or research, in this case)◦ Maintaining a high profile for safety in meetings◦ Personal attendance of managers at safety meetings and in walk-abouts◦ Face-to-face meetings with employees that feature safety as a topic◦ Job descriptions that include safety contracts◦ Communication about safety issues (both formal and informal)◦ Regular communication between management, supervisors and the workforce

Involvement of employees, including:◦ Empowerment◦ Delegation of responsibility for safety◦ Encouraging commitment to the organization.

Developing a “Safety Culture”


Encourage PI commitment to safety (new PI interviews?) Setting a good example (e.g., wearing PPE) Setting aside a few minutes in lab meetings to discuss safety

issues or staff concerns about safety Promote reporting of incidents (non-punitive) Upper management support (written commitment to safety

for the School, signed by the Dean, and posted) Reward good safety practices (certificates for good lab audits

or reporting unsafe practices) Self-audits of lab areas by staff (with PI involvement)

How could that work here?


Must occur for rDNA, frequency is determined by IBC (should be in writing)

SA – committed to quarterly? Recommend all labs inspected at

least annually◦ Safety technicians can be trained

to do lab audits, supervised by the BSO Checklists – can use ones provided

by CDC on SA website, or make your own. Need to document audits, notification of deficiencies, corrective action.

◦ Labs can do self-audits (documented) to increase frequency of inspections and buy in to “safety culture” Provide checklists

◦ Fire dept. weekly inspections Could be used to cover many of

the labs that need inspection

◦ Scheduled vs. drop-in?◦ Start audit program with sister

campuses◦ Summer worker? Could be

trained to do audits◦ Team audits with radiation,

fire, etc. (safety in numbers)

Recurring internal lab audits


Follow up:◦ Near misses◦ Spills◦ Releases◦ Any report of loss or release to a govt. agency◦ Lab associated infection◦ Noted deficiencies after previous inspection◦ Fire department observations while doing rounds

New PI (after orientation and lab setup) New agent in use Change-over of lab

Inspections


Should be non-confrontational but thorough Should be documented (spreadsheets/databases

available for this) Provide solutions for most common deficiencies at the

time of the audit◦ Carry vacuum setup diagram for lab vacuum◦ List of appropriate disinfectants◦ Extra signage for doors◦ Handout on proper sharps disposal

Inspections


Repeat offenders, or labs that do not correct deficiencies◦ Attempt to correct any IDLH situations before you

leave◦ Arrange meeting with PI, EHS Manager, if necessary◦ IBC policy on this issue would help

Some institutions give additional time to correct deficiencies, then escalate it to the Dept. Chair, and if necessary, to the Dean Must be published for PIs to read in advance (Safety

Bulletin?) Need upper administration buy in

Difficult Issues


Eating/drinking in the lab◦ Definitely a no-no and hard to defend◦ An easy catch for regulators◦ Includes drinks on desks in the lab,

unless there is a wall with a door◦ PIs have to enforce◦ Carry a copy of a LAI that was

contracted via ingestion – hand out to violators?

Drinking water dispenser in the lab

Some Common Observations


PPE Issues◦ A tough nut to crack in most academic institutions, but not impossible

Carry pairs of safety glasses on inspections and hand out if they cannot produce them?

Information on how to order safety glasses Remind them that eyes cannot be replaced Compliance is possible. Industry is able to get 99% compliance, but only after

working on the “safety culture” and enforcing use of PPE by putting a letter in the file of offenders, followed by probation for repeat offenders

◦ Even at BSL-1, safety glasses should be worn for any manipulation involving chemicals or organisms Eye infection from a yeast culture in the lab Do not want common lab chemicals in eyes (bleach, 7X, SDS, etc.)

Common Observations


BSC issues◦Moldy collection flasks

Carry copy of flask setup and disinfectant suggestions

Remind them that good science (i.e., tissue culture) depends on scrupulous cleaning.

Collection flasks should be plastic or have tape or netting on them, and if they are under the BSC, they should be in a plastic pan (secondary containment).

Common Observations


Sharps (such as Pasteur pipets) in regular trash◦ Carry a handout on proper sharps disposal◦ Provide a small poster to be posted in the labs (with pictures) that

summarizes disposal of broken glass, sharps, glass tubes, etc. Expired BSC certifications◦ Hands on training should include teaching staff to check Magnahelic

gauge and last certification date before working inside BSC◦ Different way to handle annual certification – many institutions do not

leave this up to the PIs. They have a program that tracks the dates (in Maintenance or EHS) and prompts for annual testing.

Observations


Young children in the labs ◦ Definitely not in the “business” area of the

lab. May be acceptable if they are in an office with a door. Concerns are chemical as well as biological. There should be a written policy about where children can go.

Cloth chairs◦ BMBL – even at BSL-1, chairs must be

impermeable and able to be disinfected Quick fix – cover with a heavy duty plastic

bag or duct tape until chair can be replaced

Observations


◦ Dirty BSCs Training course should discuss routine lab cleaning and

include monthly wipe down of BSC, including under work surface (if removable)

Many problems avoided by cleaning/disinfecting BSC thoroughly (walls, glass, work surface) before and after work. Use a “Swiffer” duster.

All equipment going into the BSC is wiped down with alcohol or disinfectant.

All items coming out of the BSC after work is done are decontaminated with an appropriate disinfectant.

Chemicals and other items should not be stored in the BSC

Common Observations


Lab equipment and surfaces◦Monthly decontamination of water baths

and incubators Discard old cultures After any spill, for sure Follow manufacturers instructions, or use

disinfectant followed by alcohol or sterile water

◦ Daily wipedown of bench tops◦Who cleans the floors?

Use appropriate detergent disinfectant, such as Vesphene

Common Observations


Training of lab staff◦ Ask to see their SOPs for lab tasks or equipment operation◦ Ask to see the documentation that the SOPs were read

Is there a copy of the research proposal(s) available in the lab, and have the employees doing the research signed off that they have read it?◦ Various agencies conduct interviews to determine if

PI and/or staff are informed. This is an easy catch for a regulator.

The staff should be able to describe the spill procedure, who to notify, where to go to report an exposure, etc.◦ Ask informal questions during your visits to test their

understanding◦ Post emergency procedures in lab (spills, exposures, etc.)

Observations


Should have a biohazard symbol and the word “Biohazard” List contact information for lab, including a night contact

◦ Can Security contact PI at home if they have a name to call? Should list Biosafety Level, infectious agents in use (BSL-2 and

above), human-sourced products, etc.◦ Unless security is a concern, SA may not have to be listed, but

since building is secured, this should not be a big issue List any special entry requirements or concerns, e.g.,

◦ Need a respirator when work is ongoing◦ Vaccinations needed to enter◦ Agent may put pregnant or immune suppressed person at

increased risk◦ Anyone entering should have Occupational Health approval

Door Signage


Disinfection◦ List of appropriate disinfectants included in Biosafety Manual

Should be based off of EPA Approved lists, and targeted for type of organism as well as application

It is illegal to use/prepare disinfectants in opposition to label claims E.g., using on porous surfaces when claims are for hard surfaces or not

using on precleaned surfaces Alcohol is not an appropriate disinfectant for most infectious

agents OSHA will cite you for using alcohol with human sourced materials Alcohol is appropriate for controlling environmental contamination on

clean surfaces Wiping down materials going into a BSC, etc.

Disinfection


For BBP and most infectious agents, use:◦ List B (tuberculocides)◦ List A Sterilants◦ List D, List E (eff vs. TB, HBV)

Commonly used:◦ 2 -10% bleach (@5.25% NaOCl)◦ Cavicide, Citrex, Amphyl, Dispatch◦ “Lysol” has many different

formulations – make sure you are using one that is tuberculocidal

Floors: Vesphene, LpH Hand sanitizers do not

belong next to the sink!

Disinfection

Disinfection website:http://www.epa.gov/oppad001/chemregindex.htm

http://www.epa.gov/oppad001/chemregindex.htm


Classroom Training Should provide copies of slides so those that may

not understand immediately can have a reference Exercises and ice-breakers to keep people focused◦ Gameshow Pro game – load your own questions, force

audience participation◦ Crossword puzzle, fill in the blank, break into groups and

discuss an issue, case studies, etc. Lab Associated Infection case study◦ Have trainees point out all of the mistakes that

were made◦ Use to reinforce timely reporting, knowing signs and

symptoms, use of PPE, etc.


AAALAC demanded animal handler training sessions for all infectious agents in the facility

Training of animal handlers (in a group) is a good way to get to know them so they feel comfortable telling you about their concerns

Game format works well (Gameshow Pro or manual game of Jeopardy or Tic-Tac-Toe)◦ Hand out candy as prizes (they will remember you)

Animal Handler Training


Handouts written in layman’s terms (esp. for infectious agents – modify Canadian MSDS to focus on mode of transmission, signs and symptoms, incubation period)◦ Give them your phone # and e-mail address

on the handouts Keep it fun and interesting Document all session attendance

Animal Handler Training


4 hour classroom for all BSL2, 8 hour classroom for all BSL3, including all new MDs, PIs, grad students, etc.◦ Minimum 6 hours hands-on

EHS training for all BSL3◦ BSL2 hands-on offered --

mandatory for SA work 12 page test for BSL3, 4

page test for BSL2

BSL3 workers – ◦ Mandatory verbal test with RO

covering all emergency procedures, spills, exposure reporting, BMBL, agent specific info, etc.

Voluntary serum banking, medical surveillance, mental fitness check

UTMB Training Program


Even experienced PIs, MDs, etc. may have marginal technique◦ Some non-nationals may not have had much

lab experience, or may not have used appropriate equipment

Making training mandatory for everyone (BSL-3) gives a baseline of institutional expectations and eliminates feeling of being singled out◦ People will know what they are supposed to be

doing, even if they may choose not to do it

Hands-on Training


Focus on use of BSC◦ Cleaning and decontamination of BSC, placement of

equipment, hand movements, decon of equipment, entering and leaving BSC, spills in the cabinet

Table-top exercises for centrifuge spills and leaks, spills in the lab, demonstration of BSC airflow with smoke stick or machine

Use of PPE, training on PAPR (if appropriate) and wearing PAPR while working in the BSC during the training

UTMB Hands-On training


Trainee given new safety glasses to keep, appropriate PPE

Simple lab experiment (serial dilution) given to trainee, who does it with their normal technique, observed by the biosafety trainer (~2 hours)◦ Usually use diluted fluorescein as

“virus” for procedure Lapses in technique discussed with

trainee Black light can be used to point out

aerosols, drips, etc.

Next, trainee comes back another day and performs a similar experiment, attempting to correct procedure based on trainer comments

Trainee returns at least one more time to work, ideally with good technique.

Trainee may have to come back for additional sessions until they have mastered use of the BSC, able to answer questions about spills, cleanup, use of centrifuges, etc.

Hands-on Procedure


Select Agents/Toxins


73.9 Responsible Official◦Have authority and

responsibility to act on behalf of the institution

◦ Ensure compliance◦Document annual

inspections and correct deficiencies

◦May designate alternate

73.10 Restricting Access and SRAs◦Access

Possession or the ability to gain possession

Do you have access defined in your document?

No access with approved SRA

Can request expedited approval

Can appeal denial Valid for a max. of 5 years

Select Agent


Physical security Inventory control Information systems control Access control Routine cleaning, maintenance,

repairs Removing unauthorized or

suspicious persons Badge, key and card control Reporting Training Drilled and reviewed annually

SA Security 73.11 Security◦ Develop and implement a

written security plan Site specific risk assessment Provide graded protection in

accordance with the risk


Only individuals with approved SRA have unescorted access

Unapproved individuals are continuously escorted by an approved individual

Separate SA from the public areas

Storage containers are secured

Inspect all suspicious packages

Establish a protocol for intra-entity transfers

Prohibit sharing pins, keycards, passwords

Plan for how/who will receive packages of SA

Security


The RO will be immediately notified:◦ Loss or compromise of

keys, passwords, combination

◦ Suspicious persons/activities

◦ Loss or theft of SA◦Release of SA◦ Inventory record

alteration or discrepancy

SA Security


Written Biosafety Plan Describe the biosafety

and containment procedures sufficient to contain the SA or toxin◦ Physical structure◦Operational and

procedural safeguards

Consider ◦BMBL◦OHSA 29 CFR parts 1910.

1200 (HazCom) and 1910.1450 (Occ Exp to Hazardous Chemicals)

◦NIH Guidelines for rDNA Annual drills/exercises

to test plan◦Revise as necessary

SA Biosafety 73.12


Need approval from CDC or USDA for◦ Transfer of a drug

resistance◦Biosynthesis of select

toxins with LD50<100ng/kg body weight

Restricted Experiments (SA) 73.13


Written Incident Response Plan◦ Coordinated with any entity-

wide plans◦ Kept in the workplace and

available to employees for review

◦ Drills/exercises held annually

Entity’s response procedures for:◦ Theft, loss, release ◦ Inventory discrepancies◦ Security breaches (including

information systems◦ Severe weather and natural

disasters◦ Workplace violence◦ Bomb threats◦ Suspicious packages◦ Emergencies (fire, gas leak,

explosion, power outage)

73.14 Incident Response


The response procedures must account for:◦ Hazards associated with the SA

or toxin◦ Appropriate actions to contain

the SA/toxin Name and contact info for

key individuals◦ Backup for people on vacation,

ill

Personnel roles, lines of authority and communication

Emergency medical treatment and First Aid

PPE and emergency equipment

Site security and control Procedures for emergency

evacuation Decontamination

procedures

Incident Response Plan


Provide training prior to access

Training address:◦ Particular needs of the

individual◦ The work they will do◦ The risks posed by the SA

Annual refresher training Training records maintained

73.15 Training


CDC or APHIS must authorize all transfers◦ Form 2

Transfer only to registered entities/individuals◦ The sender is either registered

for the SA/toxin, is exempt, or is outside the US and meets all import requirements

◦ The recipient must be registered for the SA or toxin

73.16 Transfers


Accurate, current inventory for each SA held in long term storage◦ Guidance on CDC website for

definition of “long term storage”

List of approved individuals Record of all entries into SA

areas

Accurate, current records associated with◦ RO, Security, Biosafety,

Incident Response, Training sections

Written explanation of any discrepancies

Ensure that all records and databases are accurate, have controlled access, and authenticity may be verified

Maintain for 3 years

73.17 Records


When?◦Without prior notification ◦ Prior to issuing a certificate of registration

73.18 Inspections


Immediately notify CDC or APHIS for:◦ Theft or loss of SA or toxin◦ Release of an agent causing occupational exposure or outside

the primary barriers of the biocontainment area Some people regard this as a spill outside the BSC, if this is the

primary biocontainment area Notifications that are overly cautious are preferred to no

notifications. They would rather know about anything you are unsure about.

73.19 Notification of Theft, Loss or Release


73.20 Administrative Review◦ Person or entity my

appeal a denial, revocation, suspension, limitation or revocation in writing if submitted within 30 days

73.21 Civil Money Penalties

The Inspector General (DHHS only) is the delegated authority to conduct investigations and to impose civil money penalties against any individual or entity for violations

Review and Penalties


Updates on the CDC Select Agent home page◦ http://

www.selectagents.gov/index.html

Biosafety Listserve notices of changes and proposals

Bill to move Select Agent process under Homeland Security

SA Updates


Info from Texas Society for Biomedical Research meeting◦ Southwest Foundation (San Antonio)

Deficiencies in training and inventory system Implemented a computerized bar-coding system

for identifying all vials of SA Implemented a computer based training and

tracking system

Select Agent Inspection

Research at SW Foundation


Present outline of course training topics Define record keeping requirements ensuring

compliance Refresher training annually “Means used to verify that the employee

understood the training”◦Quiz with passing grade and retraining on missed

questions GAP notification for training due/missed Provide “Proficiency Statement” and/or Training

Certificate for completed training modules

SA Training Requirements


Inventory discrepancies --common citation◦ Provide form to researchers

(examples on internet)◦ BSO or staff should do spot

checks of inventory (Quarterly?)

SA Inventory


ABSA involvement and meeting attendance◦ Keep up with current issues◦Make contacts that last a lifetime◦ Find a mentor for new projects◦ Attend courses to broaden knowledge and

fulfill continuing education requirements Local affiliate (MABSA)◦ CM credits for meetings/seminars

RBP ◦Will be required to recertify every 5 years with 40 points,

similar to CBSPs

Biosafety Profession


Sign up for MMWR (Morbidity and Mortality Weekly Reports) from CDC. Free, interesting and sent via e-mail (http://www.cdc.gov/mmwr/)

Read ABSA Journal for notices, research into biosafety issues

List Serve – don’t need to read everything, but often there are timely notices of legislation, news items, etc.

NIH outreach sessions◦ Keep up with NIH proposed

regulations, interpretations of the guidelines

Staying on top of it all:

http://www.cdc.gov/mmwr/


Ryan Burnette, Ph.D.Director9011 Arboretum Parkway, Suite 310Richmond, VA 23236866-654-6674www.AllianceBiosciences.cominfo@AllianceBiosciences.com

Contact


http://www.alliancebiosciences.com/

Documents

Www.AllianceBiosciences.com Malcolm Barth, Ph.D. Marian Downing, RBP, CBSP, SM(NRCM) Ryan Burnette, Ph.D., Director Biosafety Program Management Refresher